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Kamergrauzis A, Pilmane M, Junga A. Human Defence Factors in Different Gestational Week Placenta: A Pilot Study. Life (Basel) 2025; 15:86. [PMID: 39860026 PMCID: PMC11767239 DOI: 10.3390/life15010086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 01/06/2025] [Accepted: 01/09/2025] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND Numerous studies have shown the presence of multiple defence factors in placental tissue, although their role is partially understood; therefore, the aim of this study was to evaluate the expression of nuclear factor-kappa B (NF-κB); human beta-defensin 2, 3, and 4 (HBD-2,3,4); cathelicidine (LL-37); heat shock protein 60 (HSP60); and interleukin 10 (IL-10) in dissimilar gestational week placental tissue and display correlations between immunoreactive cells. METHODS A total of 15 human placental tissue samples were acquired from mothers with different gestational weeks: 28, 31, and 40. Routine staining and immunohistochemistry for the samples were executed. The evaluation of data was performed with semi-quantitative methods, and, for statistical analysis, the Kruskal-Wallis test was used. Spearman's rank correlation was used for calculating correlations. RESULTS NF-κB, HBD- 2,3,4, HSP60, and IL-10 expression were discovered in every examined placental tissue cell type. LL-37 expression was found only in Hofbauer cells. A rise in expression with higher gestational weeks was noted in LL-37-positive Hofbauer cells (p = 0.03), HBD-3-positive cytotrophoblasts (p = 0.007), endothelial cells (p = 0.024), extraembryonic mesodermal cells (p = 0.004), and HBD-4-positive endothelial cells (p = 0.001). Numerous statistically significant moderate and strong positive correlations between defence factors were discovered. CONCLUSIONS The persistence of Hofbauer cell accumulations underlines the growing significance of placental macrophages in placental protection. The expression of positive defence factors and a rise in expression in tissue protection factors (HBD-3, LL-37, HBD-4) in higher gestational weeks may indicate these factors as the most significant protectors of the placenta in ontogenetic aspects. The high number of statistically significant positive and negative correlations between positive cells show a strong network to sustain distressed placental growth and therefore pregnancy.
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Affiliation(s)
| | - Mara Pilmane
- Institute of Anatomy and Anthropology, Riga Stradins University, Kronvalda Boulevard 9, LV-1010 Riga, Latvia; (A.K.); (A.J.)
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Henriksson HB, Hellström A, Nilsson AK, Sjöbom U, Jönsson B, Frändberg S. Bacterial species in cord blood and their significance in the context of clinical use. Transfus Apher Sci 2024; 63:103961. [PMID: 38981148 DOI: 10.1016/j.transci.2024.103961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 06/12/2024] [Accepted: 06/14/2024] [Indexed: 07/11/2024]
Abstract
Approximately 90 % of infants born before 28 full weeks(extremely-preterm-infants) receive erythrocyte transfusions in early life. Umbilical cord blood(UCB) has been investigated as an alternative source for erythrocyte transfusions to preterm neonates. This retrospective study aimed to compile/evaluate spectrum of bacteria groups/species intermittently detected in processed UCB at National-Swedish-Cord blood bank, (NS-CBB) during the years 2008-2020. Consecutive data from the years 2008-2020 were investigated. UCB from healthy newborns born after 37 full weeks of gestation was collected following clamping of cord (1 min) through cannulation of umbilical vein(vaginal-and C-section-deliveries). In total, 5194 cord blood units (UCBUs) that met NS-CBB-guidelines for total nucleated-cell-content(TNC) were manufactured from 8875 collections. Of 5194 UCBUs,77,6 % were from vaginal-and 22,4 % from C-section deliveries.Samples(10 mL) were collected from surplus eryhtrocyte fraction post-processing(n = 5194), transferred into BACT/ALERT® aerobic/anaerobic culture flasks and monitored 10 days using BACT/ALERT®-3D-Microbial-Detection-Systems. Positive samples were subcultured and typed for bacterial groups and/or species. Out of 5194 processed sampled UCB units,186 (3,6 %) were discarded due to positive sterility tests, 92 % were detected in samples from vaginal-deliveries and 8 % from C-section-deliveries. In all,16 different groups of bacteria and 27 species were identified. Common bacterial/groups and species were anaerobe gram-negative rods(n = 28),coagulase-negative-staphylococci(n = 21),gram-positive rods(n = 21),anaerobe-gram-positive cocci(n = 20) and viridans-streptococci(n = 13). Extracted from these results,in positive samples(n = 13) from C-section deliveries, bacteria were found:viridans-streptococci(n = 7),Aerococcus-urinae(n = 1), Staphylococcus lugdunensis(n = 1),other coagulase-negative staphylococci(n = 1) or a mix of aerobic/anaerobic bacteria(n = 3). Our results are in alignment with previously published contamination rates in processed UCBUs. Still, results point towards importance of strict microbial monitoring when manufacturing UCBUs to achieve patient-safe- products for stem-cell transplantation/transfusion.
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Affiliation(s)
- Helena Barreto Henriksson
- Department of Laboratory Medicine, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Department of Research, Development, Education and Innovation, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Ann Hellström
- The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Anders K Nilsson
- The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ulrika Sjöbom
- The Sahlgrenska Centre for Pediatric Ophthalmology Research, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Learning and Leadership for Health Care Professionals at the Institute of Health and Care Science at Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
| | - Bodil Jönsson
- Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Sofia Frändberg
- Department of Laboratory Medicine, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
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Aidoukovitch A, Bankell E, Svensson D, Nilsson BO. Vitamin D triggers hCAP18/LL-37 production: Implications for LL-37-induced human osteoblast cytotoxicity. Biochem Biophys Res Commun 2024; 712-713:149962. [PMID: 38642493 DOI: 10.1016/j.bbrc.2024.149962] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2024] [Revised: 04/15/2024] [Accepted: 04/16/2024] [Indexed: 04/22/2024]
Abstract
The human cathelicidin LL-37 shows activity against microorganisms, but it is also cytotoxic to host cells. The CAMP gene codes for the LL-37 precursor hCAP18 which is processed extracellularly to active LL-37. It has previously been shown that vitamin D stimulates CAMP gene activity, but less information is available demonstrating that vitamin D also can increase hCAP18/LL-37 protein production. Here, we show with RT-qPCR that a physiological concentration of vitamin D (50 nM) enhances CAMP mRNA levels by about 170 times in human THP-1 monocyte cells. Stimulation with 50 nM vitamin D increases hCAP18/LL-37 protein contents 3-4 times in THP-1 cell lysates demonstrated by both dot blot analysis and ELISA applying two different hCAP18/LL-37 antibodies. Treatment with the proteasome inhibitor MG132 enhances hCAP18/LL-37 levels, suggesting that turnover of hCAP18/LL-37 protein is regulated by the proteasome. The hCAP18/LL-37 concentration in vitamin D-stimulated THP-1 cells corresponds to 1.04 μM LL-37. Interestingly, synthetic LL-37, at this concentration, reduces viability of human osteoblast-like MG63 cells, whereas the THP-1 cells are less sensitive as demonstrated by the MTT assay. In summary, we show that vitamin D enhances hCAP18/LL-37 production, and that this effect can be of physiological/pathophysiological relevance for LL-37-induced human osteoblast toxicity.
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Affiliation(s)
- Alexandra Aidoukovitch
- Department of Experimental Medical Science, Lund University, BMC D12, SE-22184, Lund, Sweden
| | - Elisabeth Bankell
- Department of Experimental Medical Science, Lund University, BMC D12, SE-22184, Lund, Sweden
| | - Daniel Svensson
- Department of Experimental Medical Science, Lund University, BMC D12, SE-22184, Lund, Sweden
| | - Bengt-Olof Nilsson
- Department of Experimental Medical Science, Lund University, BMC D12, SE-22184, Lund, Sweden.
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Kurtović M, Piteša N, Čonkaš J, Hajpek H, Vučić M, Musani V, Ozretić P, Sabol M. GLI Transcriptional Targets S100A7 and KRT16 Show Upregulated Expression Patterns in Epidermis Overlying the Tumor Mass in Melanoma Samples. Int J Mol Sci 2024; 25:6084. [PMID: 38892279 PMCID: PMC11172526 DOI: 10.3390/ijms25116084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 05/27/2024] [Accepted: 05/28/2024] [Indexed: 06/01/2024] Open
Abstract
Although not completely understood, the role of the Hedgehog-GLI (HH-GLI) signaling pathway in melanoma and epithelial skin tumors has been reported before. In this study, we confirmed in various melanoma cell line models that keratin 16 (KRT16) and S100 Calcium-Binding Protein A7 (S100A7) are transcriptional targets of GLI Family Zinc Finger (GLI) proteins. Besides their important role in protecting and maintaining the epidermal barrier, keratins are somehow tightly connected with the S100 family of proteins. We found that stronger expression of KRT16 indeed corresponds to stronger expression of S100A7 in our clinical melanoma samples. We also report a trend regarding staining of GLI1, which corresponds to stronger staining of GLI3, KRT16, and S100A7 proteins. The most interesting of our findings is that all the proteins are detected specifically in the epidermis overlying the tumor, but rarely in the tumor itself. The examined proteins were also not detected in the healthy epidermis at the edges of the sample, suggesting that the staining is specific to the epidermis overlaying the tumor mass. Of all proteins, only S100A7 demonstrated a statistically significant trend regarding tumor staging and staining intensity. Results from our clinical samples prove that immune infiltration is an important feature of melanoma. Pigmentophages and tumor-infiltrating lymphocytes (TIL) demonstrate a significant association with tumor stage, while mononuclear cells are equally present in all stages. For S100A7, we found an association between the number of TILs and staining intensity. Considering these new findings presented in our study, we suggest a more detailed examination of the possible role of the S100A7 protein as a biomarker in melanoma.
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Affiliation(s)
- Matea Kurtović
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia; (M.K.); (N.P.); (J.Č.); (H.H.); (V.M.); (P.O.)
| | - Nikolina Piteša
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia; (M.K.); (N.P.); (J.Č.); (H.H.); (V.M.); (P.O.)
| | - Josipa Čonkaš
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia; (M.K.); (N.P.); (J.Č.); (H.H.); (V.M.); (P.O.)
| | - Helena Hajpek
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia; (M.K.); (N.P.); (J.Č.); (H.H.); (V.M.); (P.O.)
- Department of Biology, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia
| | - Majda Vučić
- Ljudevit Jurak Clinical Department of Pathology and Cytology, Sestre Milosrdnice University Hospital Center, 10000 Zagreb, Croatia;
- Department of Pathology, School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia
| | - Vesna Musani
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia; (M.K.); (N.P.); (J.Č.); (H.H.); (V.M.); (P.O.)
| | - Petar Ozretić
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia; (M.K.); (N.P.); (J.Č.); (H.H.); (V.M.); (P.O.)
| | - Maja Sabol
- Division of Molecular Medicine, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia; (M.K.); (N.P.); (J.Č.); (H.H.); (V.M.); (P.O.)
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Suárez JAG, Calumby RJN, Silva DP, Barbosa VT, Maranhão FCA, Moreira IF, Melhem MSC, Moreira RTF. Neonatal innate immunity response in invasive candidiasis. BRAZ J BIOL 2024; 84:e275155. [PMID: 38808781 DOI: 10.1590/1519-6984.275155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 03/18/2024] [Indexed: 05/30/2024] Open
Abstract
Infections caused by Candida spp. are frequent in critically hospitalized patients, especially among premature neonates, representing one of the most common healthcare-related infections. Although there is considerable production of current knowledge about the mechanisms of immune response, aspects involved in the newborn's innate defense are not fully understood. The aim of this study was to describe the innate immune mechanisms involved in the defense of neonates against invasive candidiasis. This is an integrative literature review from the Scopus, Scifinder, Medline, Web of Science databases and the electronic libraries ScienceDirect and Scielo, in the period between 2002 and 2020, with rescue based on primary descriptor Immunity Innate plus secondary descriptors Candidiasis Invasive AND Infant Newborn. We have observed the involvement of various mechanisms in the neonatal response against invasive candidiasis, including the recognition, signaling, recruitment, and initiation of an effective immune response. These mechanisms encompass the presence of antimicrobial peptides, phagocytosis, synthesis of reactive oxygen species, inflammatory mediators, and complex cell signaling systems mediated by Pattern Recognition Receptors (PRRs). With this study, it is expected to contribute to the expansion of knowledge about the immunological mechanisms involved in the innate immune response of the newborn against disseminated infections caused by Candida species, and in the same sense, highlight the importance of this knowledge as a reflex in the decrease in mortality in the neonatal period.
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Affiliation(s)
- J A G Suárez
- Universidade Federal de Ouro Preto - UFOP, Ouro Preto, MG, Brasil
| | - R J N Calumby
- Universidade Federal de Alagoas - UFAL, Campus A. C. Simões, Maceió, AL, Brasil
| | - D P Silva
- Universidade Federal de Alagoas - UFAL, Campus A. C. Simões, Maceió, AL, Brasil
| | - V T Barbosa
- Universidade Federal de Alagoas - UFAL, Campus A. C. Simões, Maceió, AL, Brasil
| | - F C A Maranhão
- Universidade Federal de Alagoas - UFAL, Campus A. C. Simões, Maceió, AL, Brasil
| | - I F Moreira
- Universidade Federal de Alagoas - UFAL, Campus A. C. Simões, Maceió, AL, Brasil
| | - M S C Melhem
- Universidade Federal de Mato Grosso do Sul - UFMS, Faculdade de Medicina, Programa de Pós Graduação em Doenças Infecciosas, Campo Grande, MS, Brasil
| | - R T F Moreira
- Universidade Federal de Alagoas - UFAL, Campus A. C. Simões, Maceió, AL, Brasil
- Universidade Federal de Mato Grosso do Sul - UFMS, Faculdade de Medicina, Programa de Pós Graduação em Doenças Infecciosas, Campo Grande, MS, Brasil
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Myszor IT, Lapka K, Hermannsson K, Rekha RS, Bergman P, Gudmundsson GH. Bile acid metabolites enhance expression of cathelicidin antimicrobial peptide in airway epithelium through activation of the TGR5-ERK1/2 pathway. Sci Rep 2024; 14:6750. [PMID: 38514730 PMCID: PMC10957955 DOI: 10.1038/s41598-024-57251-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 03/15/2024] [Indexed: 03/23/2024] Open
Abstract
Signals for the maintenance of epithelial homeostasis are provided in part by commensal bacteria metabolites, that promote tissue homeostasis in the gut and remote organs as microbiota metabolites enter the bloodstream. In our study, we investigated the effects of bile acid metabolites, 3-oxolithocholic acid (3-oxoLCA), alloisolithocholic acid (AILCA) and isolithocholic acid (ILCA) produced from lithocholic acid (LCA) by microbiota, on the regulation of innate immune responses connected to the expression of host defense peptide cathelicidin in lung epithelial cells. The bile acid metabolites enhanced expression of cathelicidin at low concentrations in human bronchial epithelial cell line BCi-NS1.1 and primary bronchial/tracheal cells (HBEpC), indicating physiological relevance for modulation of innate immunity in airway epithelium by bile acid metabolites. Our study concentrated on deciphering signaling pathways regulating expression of human cathelicidin, revealing that LCA and 3-oxoLCA activate the surface G protein-coupled bile acid receptor 1 (TGR5, Takeda-G-protein-receptor-5)-extracellular signal-regulated kinase (ERK1/2) cascade, rather than the nuclear receptors, aryl hydrocarbon receptor, farnesoid X receptor and vitamin D3 receptor in bronchial epithelium. Overall, our study provides new insights into the modulation of innate immune responses by microbiota bile acid metabolites in the gut-lung axis, highlighting the differences in epithelial responses between different tissues.
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Affiliation(s)
- Iwona T Myszor
- Faculty of Life and Environmental Sciences, Biomedical Center, University of Iceland, Reykjavik, Iceland
| | - Kornelia Lapka
- Faculty of Life and Environmental Sciences, Biomedical Center, University of Iceland, Reykjavik, Iceland
| | - Kristjan Hermannsson
- Faculty of Life and Environmental Sciences, Biomedical Center, University of Iceland, Reykjavik, Iceland
| | - Rokeya Sultana Rekha
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
- Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Peter Bergman
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
- Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Gudmundur Hrafn Gudmundsson
- Faculty of Life and Environmental Sciences, Biomedical Center, University of Iceland, Reykjavik, Iceland.
- Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.
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Kanninen T, Tao L, Romero R, Xu Y, Arenas-Hernandez M, Galaz J, Liu Z, Miller D, Levenson D, Greenberg JM, Panzer J, Padron J, Theis KR, Gomez-Lopez N. Thymic stromal lymphopoietin participates in the host response to intra-amniotic inflammation leading to preterm labor and birth. Hum Immunol 2023; 84:450-463. [PMID: 37422429 PMCID: PMC10530449 DOI: 10.1016/j.humimm.2023.06.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 06/13/2023] [Accepted: 06/26/2023] [Indexed: 07/10/2023]
Abstract
The aim of this study was to establish the role of thymic stromal lymphopoietin (TSLP) in the intra-amniotic host response of women with spontaneous preterm labor (sPTL) and birth. Amniotic fluid and chorioamniotic membranes (CAM) were collected from women with sPTL who delivered at term (n = 30) or preterm without intra-amniotic inflammation (n = 34), with sterile intra-amniotic inflammation (SIAI, n = 27), or with intra-amniotic infection (IAI, n = 17). Amnion epithelial cells (AEC), Ureaplasma parvum, and Sneathia spp. were also utilized. The expression of TSLP, TSLPR, and IL-7Rα was evaluated in amniotic fluid or CAM by RT-qPCR and/or immunoassays. AEC co-cultured with Ureaplasma parvum or Sneathia spp. were evaluated for TSLP expression by immunofluorescence and/or RT-qPCR. Our data show that TSLP was elevated in amniotic fluid of women with SIAI or IAI and expressed by the CAM. TSLPR and IL-7Rα had detectable gene and protein expression in the CAM; yet, CRLF2 was specifically elevated with IAI. While TSLP localized to all layers of the CAM and increased with SIAI or IAI, TSLPR and IL-7Rα were minimal and became most apparent with IAI. Co-culture experiments indicated that Ureaplasma parvum and Sneathia spp. differentially upregulated TSLP expression in AEC. Together, these findings indicate that TSLP is a central component of the intra-amniotic host response during sPTL.
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Affiliation(s)
- Tomi Kanninen
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, 20892 and Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Li Tao
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, 20892 and Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Roberto Romero
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, 20892 and Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI 48824, USA
| | - Yi Xu
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, 20892 and Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Marcia Arenas-Hernandez
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, 20892 and Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Jose Galaz
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, 20892 and Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago 8330024, Chile
| | - Zhenjie Liu
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, 20892 and Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Derek Miller
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, 20892 and Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Dustyn Levenson
- Wayne State University School of Medicine, Detroit, MI 48201, USA; Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Jonathan M Greenberg
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, 20892 and Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Jonathan Panzer
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, 20892 and Detroit, MI 48201, USA; Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Justin Padron
- Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Kevin R Theis
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, 20892 and Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Nardhy Gomez-Lopez
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, 20892 and Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
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8
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Wenani D, Burgoine K, Williams SLA, Musaba M, Gebremichael T, Clarke A, Blanks KJ, Nantale R, Nawanga J, Kiguli S, English M, Waiswa P, Darmstadt GL, Matovu JK, Mukunya D. Perceptions, beliefs, and current practices regarding neonatal skin care and emollient use in eastern Uganda: a qualitative study. BMC Pediatr 2023; 23:223. [PMID: 37147698 PMCID: PMC10163695 DOI: 10.1186/s12887-023-04040-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Accepted: 04/27/2023] [Indexed: 05/07/2023] Open
Abstract
BACKGROUND The skin is a major route of infection in the neonatal period, especially in low birthweight (LBW) infants. Appropriate and safe neonatal skin care practices are required to reduce this risk. The perceptions and beliefs of mothers and other caregivers towards various neonatal skin care practices in our setting have been documented. Data from Asia suggests that the application of emollient to the skin of LBW infants can promote growth, reduce serious neonatal infections, and potentially reduce mortality. This is the first study to explore the acceptability of emollients and massage as part of neonatal skin care in a low-resource setting in sub-Saharan Africa (SSA) that is representative of the majority of government health facilities in Uganda and many in SSA. OBJECTIVE To explore perceptions, beliefs, and current practices regarding neonatal skin care and emollient use in eastern Uganda. METHODS We conducted a qualitative study consisting of three focus group discussions (30 participants), eight in-depth interviews with mothers/caregivers of preterm and term neonates and 12 key informant interviews with midwives, doctors and community health workers involved in neonatal care, to explore the perceptions and practices surrounding neonatal skin care and emollient use. Data collected were transcribed and analyzed using thematic content analysis. RESULTS Mothers perceived that skin care began in utero. Skincare practices depended on the place of delivery; for deliveries in a health facility the skincare practices were mainly based on the health worker's advice. Vernix caseosa was often washed off due to its perceived undesirability and was attributed to sexual intercourse in the last trimester. Despite their deleterious attributes found in previous studies, petrolatum-based oils, petrolatum-based jellies and talcum baby powders were the most commonly reported items used in neonatal skin care. In our population, there was high acceptability of emollient therapy use; however, neonatal massage was treated with scepticism as mothers feared damaging the vulnerable neonate. Mothers suggested massage and emollient application be undertaken by health workers, if it becomes an intervention. CONCLUSIONS In eastern Uganda, the perceptions and beliefs of mothers/caregivers toward neonatal skincare influenced their practices of which some could potentially be beneficial, and others harmful. Emollient use would be easily accepted if adequate sensitisation is conducted and using the gatekeepers such as health workers.
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Affiliation(s)
- Daniel Wenani
- Department of Community and Public Health, Busitema University, Mbale, Uganda
| | - Kathy Burgoine
- Neonatal Unit, Department of Paediatrics and Child Health, Mbale Regional Referral Hospital, Mbale, Uganda.
| | | | - Milton Musaba
- Department of Obstetrics and Gynaecology, Busitema University, Mbale, Uganda
| | | | - Andrew Clarke
- Global Programmes Division, Save the Children UK, London, UK
| | - Keona Jh Blanks
- Prematurity Research Center, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA
| | - Ritah Nantale
- Department of Community and Public Health, Busitema University, Mbale, Uganda
| | - Jascenti Nawanga
- Department of Community and Public Health, Busitema University, Mbale, Uganda
| | - Sarah Kiguli
- Department of Pediatrics and Child Health, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | | | - Peter Waiswa
- Department of Health Policy Planning and Management, Makerere University School of Public Health, Kampala, Uganda
| | - Gary L Darmstadt
- Prematurity Research Center, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA
| | - Joseph Kb Matovu
- Department of Community and Public Health, Busitema University, Mbale, Uganda
- Department of Disease Control and Environmental Health, Makerere University School of Public Health, Kampala, Uganda
| | - David Mukunya
- Department of Community and Public Health, Busitema University, Mbale, Uganda
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9
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Fan X, Yuan X, Huang M, Wang C, Jiang H, Zhang X, Sun H. Goat milk powder supplemented with branched-chain fatty acid: influence on quality and microstructure. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2023; 103:2631-2640. [PMID: 36494899 DOI: 10.1002/jsfa.12379] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 11/22/2022] [Accepted: 12/10/2022] [Indexed: 06/17/2023]
Abstract
BACKGROUND Branched-chain fatty acid (BCFA) is effective in preventing and helping to treat neonatal necrotizing enterocolitis. It is essential to supplement goat-milk powder for formula-fed preterm infants with BCFA. In this study, the quality and microstructures of milk powders supplemented with different concentrations of BCFA were evaluated, using goat milk powder without BCFA as the control group (CG). RESULTS In comparison with the CG, goat milk powder supplemented with BCFA exhibited smaller fat globules and a significant drop in overall particle size. During 16 weeks of storage, BCFA-supplemented groups showed suitable moisture content and viscosity and good solubility. The BCFA also helped reduce the number of folds on the surface of the milk powder particles. CONCLUSION The findings of this study indicate that goat milk powders with BCFA exhibit differences in quality and microstructure in comparison with ordinary goat milk powder, which is relevant for the future development and application of BCFA in foods. © 2022 Society of Chemical Industry.
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Affiliation(s)
- Xiaoxue Fan
- College of Food Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Xinlu Yuan
- Class 13 Grade 2022, High School Attached To Shandong Normal University, Jinan, China
| | - Mengyao Huang
- College of Food Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Cunfang Wang
- College of Food Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Hua Jiang
- College of Food Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Xiaoning Zhang
- College of Food Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Hongyan Sun
- Research and Development Department, Linyi Gerui Food Co., Ltd, Linyi, China
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10
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Trompette A, Ubags ND. Skin barrier immunology from early life to adulthood. Mucosal Immunol 2023; 16:194-207. [PMID: 36868478 DOI: 10.1016/j.mucimm.2023.02.005] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Revised: 02/15/2023] [Accepted: 02/21/2023] [Indexed: 03/05/2023]
Abstract
Our skin has a unique barrier function, which is imperative for the body's protection against external pathogens and environmental insults. Although interacting closely and sharing many similarities with key mucosal barrier sites, such as the gut and the lung, the skin also provides protection for internal tissues and organs and has a distinct lipid and chemical composition. Skin immunity develops over time and is influenced by a multiplicity of different factors, including lifestyle, genetics, and environmental exposures. Alterations in early life skin immune and structural development may have long-term consequences for skin health. In this review, we summarize the current knowledge on cutaneous barrier and immune development from early life to adulthood, with an overview of skin physiology and immune responses. We specifically highlight the influence of the skin microenvironment and other host intrinsic, host extrinsic (e.g. skin microbiome), and environmental factors on early life cutaneous immunity.
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Affiliation(s)
- Aurélien Trompette
- Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
| | - Niki D Ubags
- Faculty of Biology and Medicine, University of Lausanne, Service de Pneumologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
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11
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Darlenski R, Fluhr JW. How do the skin barrier and microbiome adapt to the extra-uterine environment after birth? Implications for the clinical practice. Int J Cosmet Sci 2023. [PMID: 36692960 DOI: 10.1111/ics.12844] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2022] [Revised: 01/10/2023] [Accepted: 01/22/2023] [Indexed: 01/25/2023]
Abstract
The multiple protective functions of the skin derive from the interactions between epithelial skin and immune cells as well as the commensal microbiota. Developed in the last trimester of intra-uterine life, the skin barrier adapts dynamically after birth. Specific differences in the structure and physiology have been disclosed between infant and adult skin. The stratum corneum of infants is thinner and structured by thicker corneocytes with a more anisotropic surface in comparison to adult skin. Lower levels of the natural moisturizing factor and its constituents, together with the increased protease activity in the epidermis result in dry baby skin and ongoing adaptation of the desquamation to the extra-uterine environment. Infant epidermis is characterized by an accelerated proliferation rate and clinically competent permeability barrier in term neonates, despite the higher baseline values of transepidermal water loss in infants. The skin surface of newborns is less acidic, which could increase susceptibility to diaper and atopic dermatitis. Immediately after birth, skin is colonized by commensal bacteria-a process dependent on the mode of delivery and of major importance for the maturation of the immune system. Skin bacterial diversity and dysbiosis have been related to different pathology such as atopic and seborrheic dermatitis. This paper focuses on the ongoing structural, functional and biochemical adaptation of the human skin barrier after birth. We discuss the interactions on the 'skin barrier/ microbiota/ immune system' axis and their role in the development of competent functional integrity of the epidermal barrier.
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Affiliation(s)
- Razvigor Darlenski
- Department of Dermatology and Venereology, Acibadem City Clinic Tokuda Hospital Sofia, Sofia, Bulgaria.,Department of Dermatology and Venereology, Trakia University-Stara Zagora, Stara Zagora, Bulgaria
| | - Joachim W Fluhr
- Department of Dermatology, Charité Universitätsmedizin, Berlin, Germany
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12
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Antimicrobial Peptides in Early-Life Host Defense, Perinatal Infections, and Necrotizing Enterocolitis—An Update. J Clin Med 2022; 11:jcm11175074. [PMID: 36079001 PMCID: PMC9457252 DOI: 10.3390/jcm11175074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 08/21/2022] [Accepted: 08/26/2022] [Indexed: 11/17/2022] Open
Abstract
Host defense against early-life infections such as chorioamnionitis, neonatal sepsis, or necrotizing enterocolitis (NEC) relies primarily on innate immunity, in which antimicrobial peptides (AMPs) play a major role. AMPs that are important for the fetus and neonate include α and β defensins, cathelicidin LL-37, antiproteases (elafin, SLPI), and hepcidin. They can be produced by the fetus or neonate, the placenta, chorioamniotic membranes, recruited neutrophils, and milk-protein ingestion or proteolysis. They possess antimicrobial, immunomodulating, inflammation-regulating, and tissue-repairing properties. AMPs are expressed as early as the 13th week and increase progressively through gestation. Limited studies are available on AMP expression and levels in the fetus and neonate. Nevertheless, existing evidence supports the role of AMPs in pathogenesis of chorioamnionitis, neonatal sepsis, and NEC, and their association with disease severity. This suggests a potential role of AMPs in diagnosis, prevention, prognosis, and treatment of sepsis and NEC. Herein, we present an overview of the antimicrobial and immunomodulating properties of human AMPs, their sources in the intrauterine environment, fetus, and neonate, and their changes during pre- and post-natal infections and NEC. We also discuss emerging data regarding the potential utility of AMPs in early-life infections, as diagnostic or predictive biomarkers and as therapeutic alternatives or adjuncts to antibiotic therapy considering the increase of antibiotic resistance in neonatal intensive care units.
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13
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Stylianou A, Blanks KJH, Gibson RA, Kendall LK, English M, Williams S, Mehta R, Clarke A, Kanyuuru L, Aluvaala J, Darmstadt GL. Quantitative decision making for investment in global health intervention trials: Case study of the NEWBORN study on emollient therapy in preterm infants in Kenya. J Glob Health 2022; 12:04045. [PMID: 35972445 PMCID: PMC9185187 DOI: 10.7189/jogh.12.04045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Abstract
Background Partners from an NGO, academia, industry and government applied a tool originating in the private sector – Quantitative Decision Making (QDM) – to rigorously assess whether to invest in testing a global health intervention. The proposed NEWBORN study was designed to assess whether topical emollient therapy with sunflower seed oil in infants with very low birthweight <1500 g in Kenya would result in a significant reduction in neonatal mortality compared to standard of care. Methods The QDM process consisted of prior elicitation, modelling of prior distributions, and simulations to assess Probability of Success (PoS) via assurance calculations. Expert opinion was elicited on the probability that emollient therapy with sunflower seed oil will have any measurable benefit on neonatal mortality based on available evidence. The distribution of effect sizes was modelled and trial data simulated using Statistical Analysis System to obtain the overall assurance which represents the PoS for the planned study. A decision-making framework was then applied to characterise the ability of the study to meet pre-selected decision-making endpoints. Results There was a 47% chance of a positive outcome (defined as a significant relative reduction in mortality of ≥15%), a 45% chance of a negative outcome (defined as a significant relative reduction in mortality <10%), and an 8% chance of ending in the consider zone (ie, a mortality reduction of 10 to <15%) for infants <1500 g. Conclusions QDM is a novel tool from industry which has utility for prioritisation of investments in global health, complementing existing tools [eg, Child Health and Nutrition Research Initiative]. Results from application of QDM to the NEWBORN study suggests that it has a high probability of producing clear results. Findings encourage future formation of public-private partnerships for health.
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Affiliation(s)
- Annie Stylianou
- GlaxoSmithKline R&D, Gunnels Wood Road, Stevenage, Hertfordshire, UK
| | | | - Rachel A Gibson
- GlaxoSmithKline R&D, Gunnels Wood Road, Stevenage, Hertfordshire, UK
| | - Lindsay K Kendall
- GlaxoSmithKline R&D, Gunnels Wood Road, Stevenage, Hertfordshire, UK
| | - Mike English
- Oxford Centre for Global Health Research, Nuffield Department of Clinical Medicine, Oxford, UK
- KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya
| | | | | | | | - Lynn Kanyuuru
- Save the Children International, Kenya Country Office, Nairobi, Kenya
| | - Jalemba Aluvaala
- KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya
- Department of Paediatrics and Child Health, University of Nairobi, Nairobi, Kenya
| | - Gary L Darmstadt
- Department of Pediatrics, Stanford University School of Medicine, Stanford, California, USA
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14
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Abstract
Our skin is the interface through which we mediate lifelong interactions with our surrounding environment. Initial development of the skin's epidermis, adnexal structures, and barrier function is necessary for normal cutaneous microbial colonization, immune development, and prevention of disease. Early life microbial exposures can have unique and long-lasting impacts on skin health. The identity of neonatal skin microbes and the context in which they are first encountered, i.e., through a compromised skin barrier or in conjunction with cutaneous inflammation, can have additional short- and long-term health consequences. Here, we discuss key attributes of infant skin and endogenous and exogenous factors that shape its relationship to the early life cutaneous microbiome, with a focus on their clinical implications.
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Affiliation(s)
- Laura R Dwyer
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA
| | - Tiffany C Scharschmidt
- Department of Dermatology, University of California, San Francisco, San Francisco, CA, USA.
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15
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Olmos-Ortiz A, Hernández-Pérez M, Flores-Espinosa P, Sedano G, Helguera-Repetto AC, Villavicencio-Carrisoza Ó, Valdespino-Vazquez MY, Flores-Pliego A, Irles C, Rivas-Santiago B, Moreno-Verduzco ER, Díaz L, Zaga-Clavellina V. Compartmentalized Innate Immune Response of Human Fetal Membranes against Escherichia coli Choriodecidual Infection. Int J Mol Sci 2022; 23:ijms23062994. [PMID: 35328414 PMCID: PMC8949057 DOI: 10.3390/ijms23062994] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 02/21/2022] [Accepted: 03/02/2022] [Indexed: 12/29/2022] Open
Abstract
An infectious process into the uterine cavity represents a major endangered condition that compromises the immune privilege of the maternal-fetal unit and increases the risk for preterm birth (PTB) and premature rupture of membranes (PROM). Fetal membranes are active secretors of antimicrobial peptides (AMP), which limit bacterial growth, such as Escherichia coli. Nevertheless, the antibacterial responses displayed by chorioamniotic membranes against a choriodecidual E. coli infection have been briefly studied. The objective of this research was to characterize the profile of synthesis, activity, and spatial distribution of a broad panel of AMPs produced by fetal membranes in response to E. coli choriodecidual infection. Term human chorioamniotic membranes were mounted in a two independent compartment model in which the choriodecidual region was infected with live E. coli (1 × 105 CFU/mL). Amnion and choriodecidual AMP tissue levels and TNF-α and IL-1β secretion were measured by the enzyme-linked immunosorbent assay. The passage of bacterium through fetal membranes and their effect on structural continuity was followed for 24 h. Our results showed that E. coli infection caused a progressive mechanical disruption of the chorioamniotic membranes and an activated inflammatory environment. After the challenge, the amnion quickly (2-4 h) induced production of human beta defensins (HBD)-1, HBD-2, and LL-37. Afterwards (8-24 h), the amnion significantly produced HBD-1, HBD-2, HNP-1-3, S100A7, sPLA2, and elafin, whereas the choriodecidua induced LL-37 synthesis. Therefore, we noticed a temporal- and tissue-specific pattern regulation of the synthesis of AMPs by infected fetal membranes. However, fetal membranes were not able to contain the collagen degradation or the bacterial growth and migration despite the battery of produced AMPs, which deeply increases the risk for PTB and PROM. The mixture of recombinant HBDs at low concentrations resulted in increased bactericidal activity compared to each HBD alone in vitro, encouraging further research to study AMP combinations that may offer synergy to control drug-resistant infections in the perinatal period.
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Affiliation(s)
- Andrea Olmos-Ortiz
- Departamento de Inmunobioquímica, Instituto Nacional de Perinatología (INPer), Mexico City 11000, Mexico; (A.O.-O.); (M.H.-P.); (P.F.-E.); (G.S.); (A.C.H.-R.); (Ó.V.-C.); (A.F.-P.)
| | - Mayra Hernández-Pérez
- Departamento de Inmunobioquímica, Instituto Nacional de Perinatología (INPer), Mexico City 11000, Mexico; (A.O.-O.); (M.H.-P.); (P.F.-E.); (G.S.); (A.C.H.-R.); (Ó.V.-C.); (A.F.-P.)
| | - Pilar Flores-Espinosa
- Departamento de Inmunobioquímica, Instituto Nacional de Perinatología (INPer), Mexico City 11000, Mexico; (A.O.-O.); (M.H.-P.); (P.F.-E.); (G.S.); (A.C.H.-R.); (Ó.V.-C.); (A.F.-P.)
| | - Gabriela Sedano
- Departamento de Inmunobioquímica, Instituto Nacional de Perinatología (INPer), Mexico City 11000, Mexico; (A.O.-O.); (M.H.-P.); (P.F.-E.); (G.S.); (A.C.H.-R.); (Ó.V.-C.); (A.F.-P.)
| | - Addy Cecilia Helguera-Repetto
- Departamento de Inmunobioquímica, Instituto Nacional de Perinatología (INPer), Mexico City 11000, Mexico; (A.O.-O.); (M.H.-P.); (P.F.-E.); (G.S.); (A.C.H.-R.); (Ó.V.-C.); (A.F.-P.)
| | - Óscar Villavicencio-Carrisoza
- Departamento de Inmunobioquímica, Instituto Nacional de Perinatología (INPer), Mexico City 11000, Mexico; (A.O.-O.); (M.H.-P.); (P.F.-E.); (G.S.); (A.C.H.-R.); (Ó.V.-C.); (A.F.-P.)
| | | | - Arturo Flores-Pliego
- Departamento de Inmunobioquímica, Instituto Nacional de Perinatología (INPer), Mexico City 11000, Mexico; (A.O.-O.); (M.H.-P.); (P.F.-E.); (G.S.); (A.C.H.-R.); (Ó.V.-C.); (A.F.-P.)
| | - Claudine Irles
- Departamento de Fisiología y Desarrollo Celular, INPer, Mexico City 11000, Mexico;
| | | | | | - Lorenza Díaz
- Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico;
| | - Verónica Zaga-Clavellina
- Departamento de Fisiología y Desarrollo Celular, INPer, Mexico City 11000, Mexico;
- Correspondence: ; Tel.: +52-55-5520-9900 (ext. 478)
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16
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Pavel P, Blunder S, Moosbrugger-Martinz V, Elias PM, Dubrac S. Atopic Dermatitis: The Fate of the Fat. Int J Mol Sci 2022; 23:2121. [PMID: 35216234 PMCID: PMC8880331 DOI: 10.3390/ijms23042121] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 02/09/2022] [Accepted: 02/11/2022] [Indexed: 12/12/2022] Open
Abstract
Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease in which dry and itchy skin may develop into skin lesions. AD has a strong genetic component, as children from parents with AD have a two-fold increased chance of developing the disease. Genetic risk loci and epigenetic modifications reported in AD mainly locate to genes involved in the immune response and epidermal barrier function. However, AD pathogenesis cannot be fully explained by (epi)genetic factors since environmental triggers such as stress, pollution, microbiota, climate, and allergens also play a crucial role. Alterations of the epidermal barrier in AD, observed at all stages of the disease and which precede the development of overt skin inflammation, manifest as: dry skin; epidermal ultrastructural abnormalities, notably anomalies of the lamellar body cargo system; and abnormal epidermal lipid composition, including shorter fatty acid moieties in several lipid classes, such as ceramides and free fatty acids. Thus, a compelling question is whether AD is primarily a lipid disorder evolving into a chronic inflammatory disease due to genetic susceptibility loci in immunogenic genes. In this review, we focus on lipid abnormalities observed in the epidermis and blood of AD patients and evaluate their primary role in eliciting an inflammatory response.
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Affiliation(s)
- Petra Pavel
- Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, A-6020 Innsbruck, Austria; (P.P.); (S.B.); (V.M.-M.)
| | - Stefan Blunder
- Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, A-6020 Innsbruck, Austria; (P.P.); (S.B.); (V.M.-M.)
| | - Verena Moosbrugger-Martinz
- Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, A-6020 Innsbruck, Austria; (P.P.); (S.B.); (V.M.-M.)
| | - Peter M. Elias
- Department of Dermatology, University of California, San Francisco, CA 94115, USA;
| | - Sandrine Dubrac
- Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, A-6020 Innsbruck, Austria; (P.P.); (S.B.); (V.M.-M.)
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17
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The antimicrobial peptide LL-37 triggers release of apoptosis-inducing factor and shows direct effects on mitochondria. Biochem Biophys Rep 2022; 29:101192. [PMID: 34988298 PMCID: PMC8695256 DOI: 10.1016/j.bbrep.2021.101192] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 12/09/2021] [Accepted: 12/16/2021] [Indexed: 11/23/2022] Open
Abstract
The human antimicrobial peptide LL-37 permeabilizes the plasma membrane of host cells, but LL-37-induced direct effects on mitochondrial membrane permeability and function has not been reported. Here, we demonstrate that LL-37 is rapidly (within 20 min) internalized by human osteoblast-like MG63 cells, and that the peptide co-localizes with MitoTracker arguing for accumulation in mitochondria. Subcellular fractionation and Western blot disclose that stimulation with LL-37 (8 μM) for 2 h triggers release of the mitochondrial protein apoptosis-inducing factor (AIF) to the cytosol, whereas LL-37 causes no release of cytochrome C oxidase subunit IV of the inner mitochondrial membrane, suggesting that LL-37 affects mitochondrial membrane permeability in a specific manner. Next, we investigated release of AIF and cytochrome C from isolated mitochondria by measuring immunoreactivity by dot blot. The media of mitochondria treated with LL-37 (8 μM) for 2 h contained 50% more AIF and three times more cytochrome C than that of control mitochondria, showing that LL-37 promotes release of both AIF and cytochrome C. Moreover, in vesicles reflecting mitochondrial membrane lipid composition, LL-37 stimulates membrane permeabilization and release of tracer molecules. We conclude that LL-37 is rapidly internalized by MG63 cells and accumulates in mitochondria, and that the peptide triggers release of pro-apoptotic AIF and directly affects mitochondrial membrane structural properties.
LL-37 is internalized by osteoblast-like MG63 cells LL-37 accumulates in mitochondria LL-37 triggers release of apoptosis-inducing factor from mitochondria LL-37 permeabilizes mitochondrial membranes
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18
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Panero AJ, Hirahara AM, Podesta L, Jamali AA, Andersen W, Smith AA. Allograft Tissues. ATLAS OF INTERVENTIONAL ORTHOPEDICS PROCEDURES 2022:89-101. [DOI: 10.1016/b978-0-323-75514-6.00008-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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19
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Šket T, Ramuta TŽ, Starčič Erjavec M, Kreft ME. The Role of Innate Immune System in the Human Amniotic Membrane and Human Amniotic Fluid in Protection Against Intra-Amniotic Infections and Inflammation. Front Immunol 2021; 12:735324. [PMID: 34745106 PMCID: PMC8566738 DOI: 10.3389/fimmu.2021.735324] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 09/23/2021] [Indexed: 01/18/2023] Open
Abstract
Intra-amniotic infection and inflammation (IAI) affect fetal development and are highly associated with preterm labor and premature rupture of membranes, which often lead to adverse neonatal outcomes. Human amniotic membrane (hAM), the inner part of the amnio-chorionic membrane, protects the embryo/fetus from environmental dangers, including microbial infection. However, weakened amnio-chorionic membrane may be breached or pathogens may enter through a different route, leading to IAI. The hAM and human amniotic fluid (hAF) respond by activation of all components of the innate immune system. This includes changes in 1) hAM structure, 2) presence of immune cells, 3) pattern recognition receptors, 4) cytokines, 5) antimicrobial peptides, 6) lipid derivatives, and 7) complement system. Herein we provide a comprehensive and integrative review of the current understanding of the innate immune response in the hAM and hAF, which will aid in design of novel studies that may lead to breakthroughs in how we perceive the IAI.
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Affiliation(s)
- Tina Šket
- Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia
| | - Taja Železnik Ramuta
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | | | - Mateja Erdani Kreft
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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Son GH, Lee JJ, Kim Y, Lee KY. The Role of Antimicrobial Peptides in Preterm Birth. Int J Mol Sci 2021; 22:ijms22168905. [PMID: 34445608 PMCID: PMC8396209 DOI: 10.3390/ijms22168905] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 08/13/2021] [Accepted: 08/16/2021] [Indexed: 12/12/2022] Open
Abstract
Antimicrobial peptides (AMPs) are short cationic amphipathic peptides with a wide range of antimicrobial properties and play an important role in the maintenance of immune homeostasis by modulating immune responses in the reproductive tract. As intra-amniotic infection and microbial dysbiosis emerge as common causes of preterm births (PTBs), a better understanding of the AMPs involved in the development of PTB is essential. The altered expression of AMPs has been reported in PTB-related clinical presentations, such as preterm labor, intra-amniotic infection/inflammation, premature rupture of membranes, and cervical insufficiency. Moreover, it was previously reported that dysregulation of AMPs may affect the pregnancy prognosis. This review aims to describe the expression of AMPs associated with PTBs and to provide new perspectives on the role of AMPs in PTB.
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Affiliation(s)
- Ga-Hyun Son
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul 07441, Korea;
- Institute of New Frontier Research Team, College of Medicine, Hallym University, Chuncheon 24523, Korea; (J.-J.L.); (Y.K.)
- Correspondence: ; Tel.: +82-2-6960-1205
| | - Jae-Jun Lee
- Institute of New Frontier Research Team, College of Medicine, Hallym University, Chuncheon 24523, Korea; (J.-J.L.); (Y.K.)
- Departments of Anesthesiology and Pain Medicine, College of Medicine, Hallym University, Chuncheon 24523, Korea
| | - Youngmi Kim
- Institute of New Frontier Research Team, College of Medicine, Hallym University, Chuncheon 24523, Korea; (J.-J.L.); (Y.K.)
| | - Keun-Young Lee
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Hallym University College of Medicine, Kangnam Sacred Heart Hospital, Seoul 07441, Korea;
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Ramuta TŽ, Šket T, Starčič Erjavec M, Kreft ME. Antimicrobial Activity of Human Fetal Membranes: From Biological Function to Clinical Use. Front Bioeng Biotechnol 2021; 9:691522. [PMID: 34136474 PMCID: PMC8201995 DOI: 10.3389/fbioe.2021.691522] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 05/04/2021] [Indexed: 12/12/2022] Open
Abstract
The fetal membranes provide a supportive environment for the growing embryo and later fetus. Due to their versatile properties, the use of fetal membranes in tissue engineering and regenerative medicine is increasing in recent years. Moreover, as microbial infections present a crucial complication in various treatments, their antimicrobial properties are gaining more attention. The antimicrobial peptides (AMPs) are secreted by cells from various perinatal derivatives, including human amnio-chorionic membrane (hACM), human amniotic membrane (hAM), and human chorionic membrane (hCM). By exhibiting antibacterial, antifungal, antiviral, and antiprotozoal activities and immunomodulatory activities, they contribute to ensuring a healthy pregnancy and preventing complications. Several research groups investigated the antimicrobial properties of hACM, hAM, and hCM and their derivatives. These studies advanced basic knowledge of antimicrobial properties of perinatal derivatives and also provided an important insight into the potential of utilizing their antimicrobial properties in a clinical setting. After surveying the studies presenting assays on antimicrobial activity of hACM, hAM, and hCM, we identified several considerations to be taken into account when planning future studies and eventual translation of fetal membranes and their derivatives as antimicrobial agents from bench to bedside. Namely, (1) the standardization of hACM, hAM, and hCM preparation to guarantee rigorous antimicrobial activity, (2) standardization of the antimicrobial susceptibility testing methods to enable comparison of results between various studies, (3) investigation of the antimicrobial properties of fetal membranes and their derivatives in the in vivo setting, and (4) designation of donor criteria that enable the optimal donor selection. By taking these considerations into account, future studies will provide crucial information that will enable reaching the optimal treatment outcomes using the fetal membranes and their derivatives as antimicrobial agents.
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Affiliation(s)
- Taja Železnik Ramuta
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Tina Šket
- Department of Synthetic Biology and Immunology, National Institute of Chemistry, Ljubljana, Slovenia
| | | | - Mateja Erdani Kreft
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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No evidence for a placental microbiome in human pregnancies at term. Am J Obstet Gynecol 2021; 224:296.e1-296.e23. [PMID: 32871131 DOI: 10.1016/j.ajog.2020.08.103] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Revised: 08/19/2020] [Accepted: 08/26/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND The placenta plays an important role in the modulation of pregnancy immunity; however, there is no consensus regarding the existence of a placental microbiome in healthy full-term pregnancies. OBJECTIVE This study aimed to investigate the existence and origin of a placental microbiome. STUDY DESIGN A cross-sectional study comparing samples (3 layers of placental tissue, amniotic fluid, vernix caseosa, and saliva, vaginal, and rectal samples) from 2 groups of full-term births: 50 women not in labor with elective cesarean deliveries and 26 with vaginal deliveries. The comparisons were performed using polymerase chain reaction amplification and DNA sequencing techniques and bacterial culture experiments. RESULTS There were no significant differences regarding background characteristics between women who delivered by elective cesarean and those who delivered vaginally. Quantitative measurements of bacterial content in all 3 placental layers (quantitative polymerase chain reaction of the 16S ribosomal RNA gene) did not show any significant difference among any of the sample types and the negative controls. Here, 16S ribosomal RNA gene sequencing of the maternal side of the placenta could not differentiate between bacteria in the placental tissue and contamination of the laboratory reagents with bacterial DNA. Probe-specific quantitative polymerase chain reaction for bacterial taxa suspected to be present in the placenta could not detect any statistically significant difference between the 2 groups. In bacterial cultures, substantially more bacteria were observed in the placenta layers from vaginal deliveries than those from cesarean deliveries. In addition, 16S ribosomal RNA gene sequencing of bacterial colonies revealed that most of the bacteria that grew on the plates were genera typically found in human skin; moreover, it revealed that placentas delivered vaginally contained a high prevalence of common vaginal bacteria. Bacterial growth inhibition experiments indicated that placental tissue may facilitate the inhibition of bacterial growth. CONCLUSION We found no evidence to support the existence of a placental microbiome in our study of 76 term pregnancies, which used polymerase chain reaction amplification and sequencing techniques and bacterial culture experiments. Incidental findings of bacterial species could be due to contamination or to low-grade bacterial presence in some locations; such bacteria do not represent a placental microbiome per se.
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Para R, Romero R, Miller D, Panaitescu B, Varrey A, Chaiworapongsa T, Hassan SS, Hsu CD, Gomez-Lopez N. Human β-defensin-3 participates in intra-amniotic host defense in women with labor at term, spontaneous preterm labor and intact membranes, and preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med 2020; 33:4117-4132. [PMID: 30999788 PMCID: PMC6800590 DOI: 10.1080/14767058.2019.1597047] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Revised: 03/09/2019] [Accepted: 03/16/2019] [Indexed: 01/16/2023]
Abstract
Objective: Human β-defensin-3 (HBD-3) has a broad spectrum of antimicrobial activity, and activity and, therefore, plays a central role in host defense mechanisms against infection. Herein, we determined whether HBD-3 was a physiological constituent of amniotic fluid during midtrimester and at term and whether the concentration of this defensin was increased in amniotic fluid of women with spontaneous preterm labor and intact membranes and those with preterm prelabor rupture of membranes (pPROM) with intra-amniotic inflammation or intra-amniotic infection.Methods: Amniotic fluid was collected from 219 women in the following groups: (1) midtrimester who delivered at term (n = 35); (2) with or without spontaneous labor at term (n = 50); (3) spontaneous preterm labor with intact membranes who delivered at term (n = 29); (4) spontaneous preterm labor with intact membranes who delivered preterm with or without intra-amniotic inflammation or intra-amniotic infection (n = 69); and (5) pPROM with or without intra-amniotic infection (n = 36). Amniotic fluid HBD-3 concentrations were determined using a sensitive and specific ELISA kit.Results: (1) HBD-3 is a physiological constituent of amniotic fluid; (2) the amniotic fluid concentration of HBD-3 did not change with gestational age (midtrimester versus term not in labor); (3) amniotic fluid concentrations of HBD-3 were higher in women with spontaneous labor at term than in those without labor; (4) in the absence of intra-amniotic inflammation, amniotic fluid concentrations of HBD-3 were similar between women with spontaneous preterm labor who delivered preterm and those who delivered at term; (5) among patients with spontaneous preterm labor who delivered preterm, amniotic fluid concentrations of HBD-3 were greater in women with intra-amniotic infection than in those without this clinical condition; (6) among patients with spontaneous preterm labor, amniotic fluid concentrations of HBD-3 were higher in women with intra-amniotic inflammation or intra-amniotic infection who delivered preterm than in those without these clinical conditions who delivered at term; and (7) women with pPROM and intra-amniotic infection had higher median amniotic fluid concentrations of HBD-3 than those without this clinical condition.Conclusion: Human β-defensin-3 is a physiological constituent of amniotic fluid and increases during the process of labor at term. Amniotic fluid concentrations of HBD-3 were increased in women with spontaneous preterm labor with intact membranes or pPROM with intra-amniotic inflammation or intra-amniotic infection, indicating that this defensin participates in the host defense mechanisms in the amniotic cavity against microorganisms or danger signals. These findings provide insight into the soluble host defense mechanisms against intra-amniotic inflammation and intra-amniotic infection.
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Affiliation(s)
- Robert Para
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U S Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan, USA
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
| | - Roberto Romero
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U S Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan, USA
- Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, USA
- Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan, USA
- Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan, USA
| | - Derek Miller
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U S Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan, USA
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
| | - Bogdan Panaitescu
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U S Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan, USA
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
| | - Aneesha Varrey
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U S Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan, USA
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
| | - Tinnakorn Chaiworapongsa
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U S Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan, USA
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
| | - Sonia S. Hassan
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U S Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan, USA
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
- Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan, USA
| | - Chaur-Dong Hsu
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
- Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan, USA
| | - Nardhy Gomez-Lopez
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U S Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan, USA
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA
- Department of Immunology, Microbiology and Biochemistry, Wayne State University School of Medicine, Detroit, Michigan, USA
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Essawi WM, El-Demerdash AS, El-Mesalamy MM, Abonorag MA. Validation of Camel's Fetal Fluids as Antimicrobial Agents. Curr Microbiol 2020; 77:1399-1404. [PMID: 32185466 DOI: 10.1007/s00284-020-01945-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 03/05/2020] [Indexed: 11/28/2022]
Abstract
The present work investigated the effect of camel's fetal fluids on a variety of bacterial and fungal pathogens. Ten samples of camel's amniotic and allantoic fluids were collected aseptically during parturition and their antimicrobial activities were evaluated by disc diffusion method and minimum inhibitory concentration (MIC) assay. The majority of tested pathogens were inhibited by both fluids up to 25% concentration. The fluids showed zones of inhibition ranging from 8 to 30 mm. The most pronounced inhibition was detected for Staphylococcus aureus, Listeria monocytogenes, Klebsiella pneumonia, and Aspergillus niger but the weak inhibition was obtained for Enterococcus faecalis, Bacillus subtilis, and Candida albicans. Also, the MIC values of amniotic fluids (0.25-2 μg/ml) against Gram-positive bacteria and yeast were lower than the values of allantoic fluids (2-8 μg/ml). But in Gram-negative bacteria and molds, the MIC values of allantoic fluids (0.5-2 μg/ml) were the lowermost. Mucor circinelloides was the only pathogen that resisted both fluids. Analysis of fluid samples revealed the presence of several factors that are known to act as antimicrobial. All tested camel's fetal fluids harbored immunoglobulins, complements, and transferrin. Lysozyme was present in only one of 10 examined samples. We firstly report the prevalence of a profound in-vitro antimicrobial activity of camel's fetal fluids. This activity encourages their use as therapeutic alternative agents to overcome multidrug resistance problems.
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Affiliation(s)
| | - Azza S El-Demerdash
- Agriculture Research Center (ARC), Animal Health Research Institute (AHRI), Zagazig, Egypt.
| | - Manal M El-Mesalamy
- Agriculture Research Center (ARC), Animal Health Research Institute (AHRI), Zagazig, Egypt
| | - Mostafa A Abonorag
- Agriculture Research Center (ARC), Animal Health Research Institute (AHRI), Dokki, Egypt
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25
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Lowry MB, Guo C, Zhang Y, Fantacone ML, Logan IE, Campbell Y, Zhang W, Le M, Indra AK, Ganguli-Indra G, Xie J, Gallo RL, Koeffler HP, Gombart AF. A mouse model for vitamin D-induced human cathelicidin antimicrobial peptide gene expression. J Steroid Biochem Mol Biol 2020; 198:105552. [PMID: 31783153 PMCID: PMC7089838 DOI: 10.1016/j.jsbmb.2019.105552] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 11/12/2019] [Accepted: 11/24/2019] [Indexed: 12/16/2022]
Abstract
In humans and other primates, 1,25(OH)2vitamin D3 regulates the expression of the cathelicidin antimicrobial peptide (CAMP) gene via toll-like receptor (TLR) signaling that activates the vitamin D pathway. Mice and other mammals lack the vitamin D response element (VDRE) in their CAMP promoters. To elucidate the biological importance of this pathway, we generated transgenic mice that carry a genomic DNA fragment encompassing the entire human CAMP gene and crossed them with Camp knockout (KO) mice. We observed expression of the human transgene in various tissues and innate immune cells. However, in mouse CAMP transgenic macrophages, TLR activation in the presence of 25(OH)D3 did not induce expression of either CAMP or CYP27B1 as would normally occur in human macrophages, reinforcing important species differences in the actions of vitamin D. Transgenic mice did show increased resistance to colonization by Salmonella typhimurium in the gut. Furthermore, the human CAMP gene restored wound healing in the skin of Camp KO mice. Topical application of 1,25(OH)2vitamin D3 to the skin of CAMP transgenic mice induced CAMP expression and increased killing of Staphylococcus aureus in a wound infection model. Our model can help elucidate the biological importance of the vitamin D-cathelicidin pathway in both pathogenic and non-pathogenic states.
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Affiliation(s)
- Malcolm B Lowry
- Department of Microbiology, Oregon State University, Corvallis, OR 97331, USA; Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
| | - Chunxiao Guo
- Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA
| | - Yang Zhang
- Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Nutrition Graduate Program, School of Biological & Population Health Sciences, College of Public Health & Human Sciences, Oregon State University, Corvallis, OR 97331, USA
| | - Mary L Fantacone
- Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA
| | - Isabelle E Logan
- Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA
| | - Yan Campbell
- Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA
| | - Weijian Zhang
- Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA
| | - Mai Le
- Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA
| | - Arup K Indra
- Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA; Knight Cancer Institute, OHSU, Portland, OR 97239, USA; Department of Dermatology, Oregon Health & Science University (OHSU), Portland, OR 97239, USA
| | - Gitali Ganguli-Indra
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA; Knight Cancer Institute, OHSU, Portland, OR 97239, USA
| | - Jingwei Xie
- Department of Surgery, Transplant & Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE 68198, USA
| | - Richard L Gallo
- Department of Dermatology, University of California San Diego, La Jolla, CA 92093, USA
| | - H Phillip Koeffler
- Division of Hematology/Oncology, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90048, USA; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore
| | - Adrian F Gombart
- Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA; Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA.
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Human host defense peptide LL-37 facilitates double-stranded RNA pro-inflammatory signaling through up-regulation of TLR3 expression in vascular smooth muscle cells. Inflamm Res 2020; 69:579-588. [PMID: 32221618 PMCID: PMC7200649 DOI: 10.1007/s00011-020-01340-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 02/28/2020] [Accepted: 03/16/2020] [Indexed: 12/19/2022] Open
Abstract
OBJECTIVE The importance of human host defense peptide LL-37 in vascular innate immunity is not understood. Here, we assess the impact of LL-37 on double-stranded RNA (dsRNA) signaling in human vascular smooth muscle cells. MATERIALS AND METHODS Cellular import of LL-37 and synthetic dsRNA (poly I:C) were investigated by immunocytochemistry and fluorescence imaging. Transcript and protein expression were determined by qPCR, ELISA and Western blot. Knockdown of TLR3 was performed by siRNA. RESULTS LL-37 was rapidly internalized, suggesting that it has intracellular actions. Co-stimulation with poly I:C and LL-37 enhanced pro-inflammatory IL-6 and MCP-1 transcripts several fold compared to treatment with poly I:C or LL-37 alone. Poly I:C increased IL-6 and MCP-1 protein production, and this effect was potentiated by LL-37. LL-37-induced stimulation of poly I:C signaling was not associated with enhanced import of poly I:C. Treatment with poly I:C and LL-37 in combination increased expression of dsRNA receptor TLR3 compared to stimulation with poly I:C or LL-37 alone. In TLR3 knockdown cells, treatment with poly I:C and LL-37 in combination had no effect on IL-6 and MCP-1 expression, showing loss of function. CONCLUSIONS LL-37 potentiates dsRNA-induced cytokine production through up-regulation of TLR3 expression representing a novel pro-inflammatory mechanism.
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27
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Al-Adwani S, Wallin C, Balhuizen MD, Veldhuizen EJA, Coorens M, Landreh M, Végvári Á, Smith ME, Qvarfordt I, Lindén A, Gräslund A, Agerberth B, Bergman P. Studies on citrullinated LL-37: detection in human airways, antibacterial effects and biophysical properties. Sci Rep 2020; 10:2376. [PMID: 32047184 PMCID: PMC7012854 DOI: 10.1038/s41598-020-59071-7] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 01/23/2020] [Indexed: 11/09/2022] Open
Abstract
Arginine residues of the antimicrobial peptide LL-37 can be citrullinated by peptidyl arginine deiminases, which reduce the positive charge of the peptide. Notably, citrullinated LL-37 has not yet been detected in human samples. In addition, functional and biophysical properties of citrullinated LL-37 are not fully explored. The aim of this study was to detect citrullinated LL-37 in human bronchoalveolar lavage (BAL) fluid and to determine antibacterial and biophysical properties of citrullinated LL-37. BAL fluid was obtained from healthy human volunteers after intra-bronchial exposure to lipopolysaccharide. Synthetic peptides were used for bacterial killing assays, transmission electron microscopy, isothermal titration calorimetry, mass-spectrometry and circular dichroism. Using targeted proteomics, we were able to detect both native and citrullinated LL-37 in BAL fluid. The citrullinated peptide did not kill Escherichia coli nor lysed human red blood cells. Both peptides had similar α-helical secondary structures but citrullinated LL-37 was more stable at higher temperatures, as shown by circular dichroism. In conclusion, citrullinated LL-37 is present in the human airways and citrullination impaired bacterial killing, indicating that a net positive charge is important for antibacterial and membrane lysing effects. It is possible that citrullination serves as a homeostatic regulator of AMP-function by alteration of key functions.
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Affiliation(s)
- Salma Al-Adwani
- Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden.,Department of Animal and Veterinary Sciences, College of Agricultural and Marine Sciences, Sultan Qaboos University, Muscat, Oman
| | - Cecilia Wallin
- Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
| | - Melanie D Balhuizen
- Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - Edwin J A Veldhuizen
- Department of Infectious Diseases and Immunology, Division of Molecular Host Defence, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - Maarten Coorens
- Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden
| | - Michael Landreh
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Ákos Végvári
- Division of Physiological Chemistry I, Department of Medical Biochemistry & Biophysics, Karolinska Institutet, Stockholm, Sweden
| | - Margaretha E Smith
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Ingemar Qvarfordt
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Anders Lindén
- Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.,Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden
| | - Astrid Gräslund
- Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden
| | - Birgitta Agerberth
- Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden
| | - Peter Bergman
- Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, Sweden. .,Infectious Disease Clinic, Immunodeficiency Unit, Karolinska University Hospital, Stockholm, Sweden.
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28
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Aidoukovitch A, Dahl S, Fält F, Nebel D, Svensson D, Tufvesson E, Nilsson B. Antimicrobial peptide LL‐37 and its pro‐form, hCAP18, in desquamated epithelial cells of human whole saliva. Eur J Oral Sci 2019; 128:1-6. [DOI: 10.1111/eos.12664] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/19/2019] [Indexed: 11/28/2022]
Affiliation(s)
- Alexandra Aidoukovitch
- Department of Experimental Medical Science Lund University Lund Sweden
- Folktandvården Skåne Lund Sweden
| | - Sara Dahl
- Department of Experimental Medical Science Lund University Lund Sweden
| | - Felicia Fält
- Department of Experimental Medical Science Lund University Lund Sweden
| | - Daniel Nebel
- Department of Experimental Medical Science Lund University Lund Sweden
| | - Daniel Svensson
- Department of Experimental Medical Science Lund University Lund Sweden
- Department of Women's and Children's Health Karolinska Institute Solna Sweden
| | - Ellen Tufvesson
- Department of Clinical Sciences Lund, Respiratory Medicine and Allergology Lund University Lund Sweden
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29
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Sulfated Glycoaminoglycans and Proteoglycan Syndecan-4 Are Involved in Membrane Fixation of LL-37 and Its Pro-Migratory Effect in Breast Cancer Cells. Biomolecules 2019; 9:biom9090481. [PMID: 31547381 PMCID: PMC6769752 DOI: 10.3390/biom9090481] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2019] [Revised: 09/03/2019] [Accepted: 09/10/2019] [Indexed: 12/11/2022] Open
Abstract
Initially characterized by its antimicrobial activities, LL-37 has also been shown to significantly contribute to tumor development. On breast cancer cell lines, LL-37 increases intracellular calcium via the TRPV2 channel and their migration via the activation of PI3K/AKT signaling. Its all-d enantiomer d-LL-37 induces similar effects, which excludes a protein-protein interaction of LL-37 in a classic ligand-receptor manner. Its net charge of +6 gave rise to the hypothesis that the peptide uses the negative charges of sulfoglycans or sialic acids to facilitate its attachment to the cell membrane and to induce its activities. Whereas several vegetal lectins, specifically attaching to sialylated or sulfated structures, blocked the activities of LL-37 on both calcium increase and cell migration, several sialidases had no effect. However, the competitive use of free sulfated glycoaminoglycans (GAGs) as chrondroitin and heparin, or treatment of the cell surface with chondroitinase and heparinase resulted in an activity loss of 50–100% for LL-37. Concordant results were obtained by blocking the synthesis of GAGs with 4-Methylumbelliferyl-β-d-xyloside, and by suppression of glycan sulfatation by sodium chlorate. Using a candidate approach by suppressing proteoglycan synthesis using RNA interference, syndecan-4 was shown to be required for the activities of LL-37 and its binding to the cell surface. This leads to the conclusion that syndecan-4, by means of sulfated GAGs, could act as a receptor for LL-37.
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Nishijima K, Yoneda M, Hirai T, Takakuwa K, Enomoto T. Biology of the vernix caseosa: A review. J Obstet Gynaecol Res 2019; 45:2145-2149. [PMID: 31507021 DOI: 10.1111/jog.14103] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Accepted: 08/14/2019] [Indexed: 12/16/2022]
Abstract
The vernix caseosa is a complex membranous structure comprising 80% water, 10% protein, and 10% lipids including barrier lipids such as ceramides, free fatty acids, phospholipids and cholesterol, synthesized partly by fetal sebaceous glands during the last trimester of pregnancy in an antero-posterior and dorsoventral manner. Because of its lipid content, vernix is hydrophobic and protects the skin from excessive water exposure during the development of the stratum corneum. The vernix caseosa has various functions during fetal transition from an intrauterine to an extrauterine environment, including lubrication of the birth canal during parturition, barrier function to prevent water loss, temperature regulation, for innate immunity and for intestinal development. This review discusses the evidence supporting the prenatal and postnatal functions of vernix caseosa, along with its structure, composition, and physical and biological characteristics. Understanding the biology of the vernix may facilitate improved care of preterm infants immediately post-partum.
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Affiliation(s)
- Koji Nishijima
- Department of Social Welfare Science, Fukui Prefectural University, Fukui, Japan.,General Center for Perinatal, Maternal and Neonatal Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - Makoto Yoneda
- Department of Social Welfare Science, Fukui Prefectural University, Fukui, Japan
| | - Takayoshi Hirai
- Department of Social Welfare Science, Fukui Prefectural University, Fukui, Japan
| | - Koichi Takakuwa
- General Center for Perinatal, Maternal and Neonatal Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan
| | - Takayuki Enomoto
- Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
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Schoch JJ, Monir RL, Satcher KG, Harris J, Triplett E, Neu J. The infantile cutaneous microbiome: A review. Pediatr Dermatol 2019; 36:574-580. [PMID: 31332846 DOI: 10.1111/pde.13870] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Recent focus on the neonatal intestinal microbiome has advanced our knowledge of the complex interplay between the intestinal barrier, the developing immune system, and commensal and pathogenic organisms. Despite the parallel role of the infant skin in serving as both a barrier and an interface for priming the immune system, large gaps exist in our understanding of the infantile cutaneous microbiome. The skin microbiome changes and matures throughout infancy, becoming more diverse and developing the site specificity known to exist in adults. Delivery method initially determines the composition of the cutaneous microbiome, though this impact appears transient. Cutaneous microbes play a critical role in immune system development, particularly during the neonatal period, and microbes and immune cells have closely intertwined, reciprocal effects. The unique structure of newborn skin influences cutaneous microbial colonization and the development of dermatologic pathology. The development of the infantile skin barrier and cutaneous microbiome contributes to future skin pathology. Atopic dermatitis flares and seborrheic dermatitis have been linked to dysbiosis, while erythema toxicum neonatorum is an immune response to the establishment of normal bacterial skin flora. Physicians who care for infants should be aware of the impact of the infantile skin microbiome and its role in the development of pathology. A better understanding of the origin and evolution of the skin microbiome will lead to more effective prevention and treatment of pediatric skin disease.
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Affiliation(s)
- Jennifer J Schoch
- Department of Dermatology, University of Florida College of Medicine, Gainesville, Florida
| | - Reesa L Monir
- University of Florida College of Medicine, Gainesville, Florida
| | - Kerrie G Satcher
- Department of Dermatology, University of Florida College of Medicine, Gainesville, Florida
| | - Jessica Harris
- Department of Dermatology, University of Florida College of Medicine, Gainesville, Florida
| | - Eric Triplett
- Department of Microbiology and Cell Science, University of Florida, Gainesvillle, Florida
| | - Josef Neu
- Department of Pediatrics, Division of Neonatology, University of Florida College of Medicine, Gainesville, Florida
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32
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Gholipourmalekabadi M, Farhadihosseinabadi B, Faraji M, Nourani MR. How preparation and preservation procedures affect the properties of amniotic membrane? How safe are the procedures? Burns 2019; 46:1254-1271. [PMID: 31445711 DOI: 10.1016/j.burns.2019.07.005] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Revised: 05/14/2019] [Accepted: 07/03/2019] [Indexed: 12/22/2022]
Abstract
Human amniotic membrane (AM) has been widely used for tissue engineering and regenerative medicine applications. AM has many favorable characteristics such as high biocompatibility, antibacterial activity, anti-scarring property, immunomodulatory effects, anti-cancer behavior and contains several growth factors that make it an excellent natural candidate for wound healing. To date, various methods have been developed to prepare, preserve, cross-link and sterilize the AM. These methods remarkably affect the morphological, physico-chemical and biological properties of AM. Optimization of an effective and safe method for preparation and preservation of AM for a specific application is critical. In this review, the isolation, different methods of preparation, preservation, cross-linking and sterilization as well as their effects on properties of AM are well discussed. For each section, at least one effective and safe protocol is described in detail.
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Affiliation(s)
- Mazaher Gholipourmalekabadi
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medicine Sciences, Tehran, Iran
| | - Behrouz Farhadihosseinabadi
- Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Faraji
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Nourani
- Chemical Injuries Research Center, Systems Biology and Poisoning Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran; Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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Shaikhutdinova RZ, Ivanov SA, Dentovskaya SV, Titareva GM, Knirel YA. Characterization of a Transposon Tn5-Generated Mutant of Yersinia pestis Defective in Lipooligosaccharide Biosynthesis. BIOCHEMISTRY (MOSCOW) 2019; 84:398-406. [PMID: 31228931 DOI: 10.1134/s0006297919040072] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
To identify Yersinia pestis genes involved in the microbe's resistance to cationic antimicrobial peptides, the strategy of random transposon mutagenesis with a Tn5 minitransposon was used, and the library was screened for detecting polymyxin B (PMB) susceptible mutants. The mutation responsible for PMB-sensitive phenotype and the lipopolysaccharide (LPS) structure were characterized for the Y. pestis strain KM218-A3. In this strain the mini-Tn5 was located in an open reading frame with the product homologous to the E. coli protein GmhB (82% identity) functioning as d-glycero-d-manno-heptose-1,7-diphosphate phosphatase. ESI FT ICR mass spectrometry of anions was used to study the structure of the unmodified LPS of Y. pestis KM218-A3, and molecules were revealed with the full-size LPS core or with two types of an incomplete core: consisting of Kdo-Kdo or Ko-Kdo disaccharides and Hep-(Kdo)-Kdo or Hep-(Ko)-Kdo trisaccharides. The performed complementation confirmed that the defect in the biological properties of the mutant strain was caused by inactivation of the gmhB gene. These findings indicated that the gmhB gene product of Y. pestis is essential for production of wild-type LPS resistant to antimicrobial peptides and serum.
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Affiliation(s)
- R Z Shaikhutdinova
- State Research Center for Applied Microbiology and Biotechnology, Obolensk, Moscow Region, 142279, Russia
| | - S A Ivanov
- State Research Center for Applied Microbiology and Biotechnology, Obolensk, Moscow Region, 142279, Russia
| | - S V Dentovskaya
- State Research Center for Applied Microbiology and Biotechnology, Obolensk, Moscow Region, 142279, Russia.
| | - G M Titareva
- State Research Center for Applied Microbiology and Biotechnology, Obolensk, Moscow Region, 142279, Russia
| | - Yu A Knirel
- Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, 119991, Russia.
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Aidoukovitch A, Anders E, Dahl S, Nebel D, Svensson D, Nilsson BO. The host defense peptide LL-37 is internalized by human periodontal ligament cells and prevents LPS-induced MCP-1 production. J Periodontal Res 2019; 54:662-670. [PMID: 31095741 DOI: 10.1111/jre.12667] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 03/15/2019] [Accepted: 04/20/2019] [Indexed: 12/21/2022]
Abstract
OBJECTIVE The human host defense peptide LL-37 both shows antimicrobial effects and modulates host cell properties. Here, we assess the effects of synthesized LL-37 on lipopolysaccharide (LPS)-induced inflammation in human periodontal ligament (PDL) cells and investigates underlying mechanisms. BACKGROUND LL-37 has been detected in the periodontal tissues, but its functional importance for PDL cell innate immune responses is not known. METHODS Human PDL cells were obtained from premolars extracted on orthodontic indications. Cellular pro-inflammatory monocyte chemoattractant protein-1 (MCP-1) mRNA expression was determined using quantitative real-time RT-PCR. MCP-1 protein production was assessed by western blot and ELISA. Internalization of LL-37 by PDL cells was visualized by immunocytochemistry. Nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-κB) activity was assessed by western blot of phosphorylated p65, phosphorylated p105, and IκBα proteins. Binding of LL-37 to PDL cell DNA was determined by isolation and purification of DNA and dot blot for LL-37 immunoreactivity. RESULTS Treatment with LL-37 (1 µmol/L) for 24 hours prevented LPS-induced stimulation of MCP-1 expression analyzed both on transcript and on protein levels. Stimulation with LL-37 (1 µmol/L) for 24 hours had no effect on toll-like receptor (TLR)2 and TLR4 transcript expression, suggesting that LL-37 acts downstream of the TLRs. Preincubation with LL-37 for 60 minutes followed by stimulation with LPS for 24 hours in the absence of LL-37 completely prevented LPS-evoked MCP-1 transcript expression, implying that LL-37 acts intracellularly and not via binding and neutralization of LPS. In PDL cells stimulated with LL-37 for 60 minutes, the peptide was internalized as demonstrated by immunocytochemistry, suggesting an intracellular mechanism of action. LL-37 immunoreactivity was observed both in the cytosol and in the nucleus. Downregulation of LPS-induced MCP-1 by LL-37 was not mediated by reduction in NF-κB activity as shown by unaltered expression of phosphorylated p65, phosphorylated p105, and IκBα NF-κB proteins in the presence of LL-37. Immunoreactivity for LL-37 was observed in PDL cell DNA treated with but not without 0.1 and 1 µmol/L LL-37 for 60 minutes in vitro. CONCLUSION LL-37 abolishes LPS-induced MCP-1 production in human PDL cells through an intracellular, NF-κB-independent mechanism which probably involves direct interaction between LL-37 and DNA.
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Affiliation(s)
- Alexandra Aidoukovitch
- Department of Experimental Medical Science, Lund University, Lund, Sweden.,Folktandvården Skåne, Lund, Sweden
| | - Emma Anders
- Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Sara Dahl
- Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Daniel Nebel
- Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Daniel Svensson
- Department of Experimental Medical Science, Lund University, Lund, Sweden.,Department of Women's and Children's Health, Karolinska Institute, Solna, Sweden
| | - Bengt-Olof Nilsson
- Department of Experimental Medical Science, Lund University, Lund, Sweden
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35
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Myszor IT, Parveen Z, Ottosson H, Bergman P, Agerberth B, Strömberg R, Gudmundsson GH. Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity. Sci Rep 2019; 9:7114. [PMID: 31068616 PMCID: PMC6506505 DOI: 10.1038/s41598-019-43350-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Accepted: 04/18/2019] [Indexed: 01/19/2023] Open
Abstract
Aroylated phenylenediamines (APDs) are novel inducers of innate immunity enhancing cathelicidin gene expression in human bronchial epithelial cell lines. Here we present two newly developed APDs and aimed at defining the response and signaling pathways for these compounds with reference to innate immunity and antimicrobial peptide (AMP) expression. Induction was initially defined with respect to dose and time and compared with the APD Entinostat (MS-275). The induction applies to several innate immunity effectors, indicating that APDs trigger a broad spectrum of antimicrobial responses. The bactericidal effect was shown in an infection model against Pseudomonas aeruginosa by estimating bacteria entering cells. Treatment with a selected APD counteracted Pseudomonas mediated disruption of epithelial integrity. This double action by inducing AMPs and enhancing epithelial integrity for one APD compound is unique and taken as a positive indication for host directed therapy (HDT). The APD effects are mediated through Signal transducer and activator of transcription 3 (STAT3) activation. Utilization of induced innate immunity to fight infections can reduce antibiotic usage, might be effective against multidrug resistant bacteria and is in line with improved stewardship in healthcare.
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Affiliation(s)
- Iwona T Myszor
- Biomedical Center, University of Iceland, Reykjavik, 101, Iceland
| | - Zahida Parveen
- Biomedical Center, University of Iceland, Reykjavik, 101, Iceland
| | - Håkan Ottosson
- Department of Biosciences and Nutrition, Karolinska Institutet, S-14183, Huddinge, Sweden
| | - Peter Bergman
- Department of Laboratory Medicine, Clinical Microbiology, Karolinska Institutet, S-14186, Huddinge, Sweden
| | - Birgitta Agerberth
- Department of Laboratory Medicine, Clinical Microbiology, Karolinska Institutet, S-14186, Huddinge, Sweden
| | - Roger Strömberg
- Department of Biosciences and Nutrition, Karolinska Institutet, S-14183, Huddinge, Sweden
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Da Silva M, Dombre C, Brionne A, Monget P, Chessé M, De Pauw M, Mills M, Combes-Soia L, Labas V, Guyot N, Nys Y, Réhault-Godbert S. The Unique Features of Proteins Depicting the Chicken Amniotic Fluid. Mol Cell Proteomics 2019; 18:S174-S190. [PMID: 29444982 PMCID: PMC6427230 DOI: 10.1074/mcp.ra117.000459] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 01/18/2018] [Indexed: 11/06/2022] Open
Abstract
In many amniotes, the amniotic fluid is depicted as a dynamic milieu that participates in the protection of the embryo (cushioning, hydration, and immunity). However, in birds, the protein profile of the amniotic fluid remains unexplored, even though its proteomic signature is predicted to differ compared with that of humans. In fact, unlike humans, chicken amniotic fluid does not collect excretory products and its protein composition strikingly changes at mid-development because of the massive inflow of egg white proteins, which are thereafter swallowed by the embryo to support its growth. Using GeLC-MS/MS and shotgun strategies, we identified 91 nonredundant proteins delineating the chicken amniotic fluid proteome at day 11 of development, before egg white transfer. These proteins were essentially associated with the metabolism of nutrients, immune response and developmental processes. Forty-eight proteins were common to both chicken and human amniotic fluids, including serum albumin, apolipoprotein A1 and alpha-fetoprotein. We further investigated the effective role of chicken amniotic fluid in innate defense and revealed that it exhibits significant antibacterial activity at day 11 of development. This antibacterial potential is drastically enhanced after egg white transfer, presumably due to lysozyme, avian beta-defensin 11, vitelline membrane outer layer protein 1, and beta-microseminoprotein-like as the most likely antibacterial candidates. Interestingly, several proteins recovered in the chicken amniotic fluid prior and after egg white transfer are uniquely found in birds (ovalbumin and related proteins X and Y, avian beta-defensin 11) or oviparous species (vitellogenins 1 and 2, riboflavin-binding protein). This study provides an integrative overview of the chicken amniotic fluid proteome and opens stimulating perspectives in deciphering the role of avian egg-specific proteins in embryonic development, including innate immunity. These proteins may constitute valuable biomarkers for poultry production to detect hazardous situations (stress, infection, etc.), that may negatively affect the development of the chicken embryo.
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Affiliation(s)
| | - Clara Dombre
- PRC, INRA, CNRS, IFCE, Université de Tours, Nouzilly 37380, France
| | | | - Philippe Monget
- PRC, INRA, CNRS, IFCE, Université de Tours, Nouzilly 37380, France
| | - Magali Chessé
- BOA, INRA, Université de Tours, 37380 Nouzilly, France
| | | | - Maryse Mills
- BOA, INRA, Université de Tours, 37380 Nouzilly, France
| | - Lucie Combes-Soia
- PRC, INRA, CNRS, IFCE, Université de Tours, Nouzilly 37380, France;; INRA, Plate-forme de Chirurgie et Imagerie pour la Recherche et l'Enseignement (CIRE), Pôle d'Analyse et d'Imagerie des Biomolécules (PAIB), F-37380 Nouzilly, France
| | - Valérie Labas
- PRC, INRA, CNRS, IFCE, Université de Tours, Nouzilly 37380, France;; INRA, Plate-forme de Chirurgie et Imagerie pour la Recherche et l'Enseignement (CIRE), Pôle d'Analyse et d'Imagerie des Biomolécules (PAIB), F-37380 Nouzilly, France
| | - Nicolas Guyot
- BOA, INRA, Université de Tours, 37380 Nouzilly, France
| | - Yves Nys
- BOA, INRA, Université de Tours, 37380 Nouzilly, France
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37
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Dahl S, Anders E, Gidlöf O, Svensson D, Nilsson BO. The host defense peptide LL-37 triggers release of nucleic acids from human mast cells. Peptides 2018; 109:39-45. [PMID: 30308233 DOI: 10.1016/j.peptides.2018.10.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 09/28/2018] [Accepted: 10/05/2018] [Indexed: 12/23/2022]
Abstract
The human host defense peptide LL-37 possesses antimicrobial activity but also affects host cell function and viability. Mast cells are involved in innate immunity but no data have been presented on effects of LL-37 on human mast cell viability and export of nucleic acids. Here, we demonstrated by immunofluorescence microscopy that synthesized LL-37 was internalized by human LAD2 mast cells and detected both in cytoplasm and nucleus. Treatment with high (4 and 10 μM) but not low (1 μM) concentrations of LL-37 for 4 h reduced cell viability assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Stimulation with 10 μM LL-37 for 4 h enhanced export of nucleic acids, total protein and lactate dehydrogenase (LDH), suggesting that both nuclear and plasma membranes are permeabilized by LL-37. Although LL-37 triggered release of nucleic acids, no extracellular trap-like structures were observed by laser scanning confocal microscopy of cells incubated with the plasma membrane impermeable nucleic acid fluorophore SYTOX-Green, indicating that LL-37 promotes export of nucleic acids but not formation of extracellular traps. On the other hand, phorbol-12-myristate-13-acetate (PMA), which is a well-known inducer of extracellular traps, stimulated export of nucleic acids and also formation of extracellular trap-like structures. However, PMA had no effect on export of either total protein or LDH. Hence, LL-37 and PMA seem to stimulate export of nucleic acids from LAD2 mast cells through different pathways. In conclusion, we demonstrate that LL-37 triggers release of nucleic acids from human mast cells but not the formation of extracellular trap-like structures.
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Affiliation(s)
- Sara Dahl
- Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Emma Anders
- Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Olof Gidlöf
- Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden
| | - Daniel Svensson
- Department of Experimental Medical Science, Lund University, Lund, Sweden; Department of Women's and Children's Health, Karolinska Institute, Solna, Sweden
| | - Bengt-Olof Nilsson
- Department of Experimental Medical Science, Lund University, Lund, Sweden.
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Varrey A, Romero R, Panaitescu B, Miller D, Chaiworapongsa T, Patwardhan M, Faro J, Pacora P, Hassan SS, Hsu CD, Gomez-Lopez N. Human β-defensin-1: A natural antimicrobial peptide present in amniotic fluid that is increased in spontaneous preterm labor with intra-amniotic infection. Am J Reprod Immunol 2018; 80:e13031. [PMID: 30101464 DOI: 10.1111/aji.13031] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Accepted: 07/16/2018] [Indexed: 12/11/2022] Open
Abstract
PROBLEM Human β-defensins (HBDs) are antimicrobial peptides that participate in the soluble innate immune mechanisms against infection. Herein, we determined whether HBD-1 was present in amniotic fluid during normal pregnancy and whether its concentrations change with intra-amniotic inflammation and/or infection. METHOD OF STUDY Amniotic fluid was collected from 219 women in the following groups: (a) midtrimester who delivered at term (n = 35); (b) term with (n = 33) or without (n = 17) labor; (c) preterm labor with intact membranes who delivered at term (n = 29) or who delivered preterm with (n = 19) and without (n = 29) intra-amniotic inflammation and infection or with intra-amniotic inflammation but without infection (n = 21); and (d) preterm prelabor rupture of membranes (pPROM) with (n = 19) and without (n = 17) intra-amniotic inflammation/infection. Amniotic fluid HBD-1 concentrations were determined using a sensitive and specific ELISA kit. RESULTS (a) HBD-1 was detectable in all amniotic fluid samples; (b) amniotic fluid concentrations of HBD-1 were changed with gestational age (midtrimester vs term no labor), being higher in midtrimester; (c) amniotic fluid concentrations of HBD-1 were similar between women with and without spontaneous labor at term; (d) among patients with spontaneous preterm labor, amniotic fluid concentrations of HBD-1 in women with intra-amniotic inflammation/infection and in those with intra-amniotic inflammation without infection were greater than in women without intra-amniotic inflammation or infection who delivered preterm or at term; and (e) the presence of intra-amniotic inflammation and infection in patients with pPROM did not change amniotic fluid concentrations of HBD-1. CONCLUSION HBD-1 is a physiological constituent of amniotic fluid that is increased in midtrimester during normal pregnancy and in the presence of culturable microorganisms in the amniotic cavity. These findings provide insight into the soluble host defense mechanisms against intra-amniotic infection.
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Affiliation(s)
- Aneesha Varrey
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan
| | - Roberto Romero
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan.,Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan.,Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, Michigan.,Center for Molecular Medicine and Genetics, Wayne State University, Detroit, Michigan
| | - Bogdan Panaitescu
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan
| | - Derek Miller
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan
| | - Tinnakorn Chaiworapongsa
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan
| | - Manasi Patwardhan
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan
| | - Jonathan Faro
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan
| | - Percy Pacora
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan
| | - Sonia S Hassan
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan.,Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan
| | - Chaur-Dong Hsu
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan
| | - Nardhy Gomez-Lopez
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Bethesda, Maryland, and Detroit, Michigan.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan.,Department of Immunology, Microbiology and Biochemistry, Wayne State University School of Medicine, Detroit, Michigan
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Sun X, Xiu F, Pan B, Li Y, Haskins JT, Shen W, Li J. Antimicrobial peptide expression in swine granulosa cells in response to lipopolysaccharide. Theriogenology 2018; 119:80-90. [PMID: 29982140 DOI: 10.1016/j.theriogenology.2018.06.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 06/15/2018] [Accepted: 06/17/2018] [Indexed: 12/19/2022]
Abstract
Antimicrobial peptides (AMP) are host defense peptides present in all species examined. The objective of the current study was to characterize the expression of a group of antimicrobial peptides in ovarian cells, and to investigate their expression response to pathogen ligands. It was found that while PG1 transcript was not detected in the ovary, the expression of BD2 is the highest in small follicle derived granulosa cells (SGC), and its expression decreases during follicular development to large follicle stage (LGC; p < 0.05). The expression of BD2 in cumulus cells also decreased from GV to MII stage of oocyte maturation. ANG4 expression increased in granulosa cells during follicular development from SGC to LGC stage (p < 0.05), although no significant difference was observed in cumulus cells from different stages of oocyte maturation. We further examined AMP expression in follicle cells treated with different toll-like receptor (TLR) ligands which mimic pathogen exposure in the ovary. Of the four TLR ligands examined, lipopolysaccharide (LPS) exposure resulted in a 11.5 fold increase of BD2 expression, and a significant decrease of LYZ in LGC. A similar response pattern in BD2 and LYZ expression was also observed in SGC. These responses of AMP expression to LPS are associated with increased TLR4 signaling pathway component in mRNA and protein level, such as MyD88 and NFkB, and pro-inflammatory cytokines/chemokines, such as IL-6, TNFα and IL-8 (p < 0.05). Our data suggest that AMPs may play a role in innate defense as well as other physiological functions during ovarian follicular development and oocyte maturation.
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Affiliation(s)
- Xiaofeng Sun
- College of Life Sciences, Qingdao Agricultural University, Qingdao, 266109, China; Department of Animal BioSciences, University of Guelph, Guelph, Ontario, Canada
| | - Fangming Xiu
- Department of Animal BioSciences, University of Guelph, Guelph, Ontario, Canada; Translational Medicine, The SickKids Research Institute, The Hospital for Sick Children, Toronto, Canada
| | - Bo Pan
- Department of Animal BioSciences, University of Guelph, Guelph, Ontario, Canada
| | - Yapeng Li
- College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, 266109, China
| | - James T Haskins
- Department of Animal BioSciences, University of Guelph, Guelph, Ontario, Canada
| | - Wei Shen
- College of Life Sciences, Qingdao Agricultural University, Qingdao, 266109, China.
| | - Julang Li
- Department of Animal BioSciences, University of Guelph, Guelph, Ontario, Canada.
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Anders E, Dahl S, Svensson D, Nilsson BO. LL-37-induced human osteoblast cytotoxicity and permeability occurs independently of cellular LL-37 uptake through clathrin-mediated endocytosis. Biochem Biophys Res Commun 2018; 501:280-285. [DOI: 10.1016/j.bbrc.2018.04.235] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 04/30/2018] [Indexed: 12/30/2022]
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Gomez-Lopez N, Romero R, Xu Y, Miller D, Leng Y, Panaitescu B, Silva P, Faro J, Alhousseini A, Gill N, Hassan SS, Hsu CD. The immunophenotype of amniotic fluid leukocytes in normal and complicated pregnancies. Am J Reprod Immunol 2018; 79:e12827. [PMID: 29500850 DOI: 10.1111/aji.12827] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2017] [Accepted: 01/25/2018] [Indexed: 12/13/2022] Open
Abstract
PROBLEM The immune cellular composition of amniotic fluid is poorly understood. Herein, we determined: 1) the immunophenotype of amniotic fluid immune cells during the second and third trimester in the absence of intra-amniotic infection/inflammation; 2) whether amniotic fluid T cells and ILCs display different phenotypical characteristics to that of peripheral cells; and 3) whether the amniotic fluid immune cells are altered in women with intra-amniotic infection/inflammation. METHOD OF STUDY Amniotic fluid samples (n = 57) were collected from 15 to 40 weeks of gestation in women without intra-amniotic infection/inflammation. Samples from women with intra-amniotic infection/inflammation were also included (n = 9). Peripheral blood mononuclear cells from healthy adults were used as controls (n = 3). Immunophenotyping was performed using flow cytometry. RESULTS In the absence of intra-amniotic infection/inflammation, the amniotic fluid contained several immune cell populations between 15 and 40 weeks. Among these immune cells: (i) T cells and ILCs were greater than B cells and natural killer (NK) cells between 15 and 30 weeks; (ii) T cells were most abundant between 15 and 30 weeks; (iii) ILCs were most abundant between 15 and 20 weeks; (iv) B cells were scarce between 15 and 20 weeks; yet, they increased and were constant after 20 weeks; (v) NK cells were greater between 15 and 30 weeks than at term; (vi) ILCs expressed high levels of RORγt, CD161, and CD103 (ie, group 3 ILCs); (vii) T cells expressed high levels of RORγt; (viii) neutrophils increased as gestation progressed; and (ix) monocytes/macrophages emerged after 20 weeks and remained constant until term. All of the amniotic fluid immune cells, except ILCs, were increased in the presence of intra-amniotic infection/inflammation. CONCLUSION The amniotic fluid harbors a diverse immune cellular composition during normal and complicated pregnancies.
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Affiliation(s)
- Nardhy Gomez-Lopez
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD and Detroit, MI, USA.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.,Department of Immunology, Microbiology and Biochemistry, Wayne State University School of Medicine, Detroit, MI, USA
| | - Roberto Romero
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD and Detroit, MI, USA.,Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA.,Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA.,Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA
| | - Yi Xu
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD and Detroit, MI, USA.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Derek Miller
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD and Detroit, MI, USA.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.,Department of Immunology, Microbiology and Biochemistry, Wayne State University School of Medicine, Detroit, MI, USA
| | - Yaozhu Leng
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD and Detroit, MI, USA.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Bogdan Panaitescu
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD and Detroit, MI, USA.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Pablo Silva
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD and Detroit, MI, USA.,Division of Obstetrics and Gynecology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Jonathan Faro
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Ali Alhousseini
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Navleen Gill
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Sonia S Hassan
- Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD and Detroit, MI, USA.,Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.,Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA
| | - Chaur-Dong Hsu
- Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA
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Jie L, Qi C, Sun J, Yu R, Wang X, Korma SA, Xiang J, Jin Q, Akoh CC, Xiao H, Wang X. The impact of lactation and gestational age on the composition of branched-chain fatty acids in human breast milk. Food Funct 2018; 9:1747-1754. [PMID: 29497729 DOI: 10.1039/c7fo01979c] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Breast milk consumption reduces the incidence of necrotizing enterocolitis (NEC) in preterm infants compared to formula. Branched-chain fatty acids (BCFAs) are present in breast milk but not in most formulas intended for preterm infants. We aimed to determine the composition of BCFAs in the breast milk of mothers with preterm infants, and to understand the impact of gestational age at birth and stage of lactation on BCFA content. The main BCFAs in preterm breast milk were iso-14:0, iso-15:0, anteiso-15:0, iso-16:0, iso-17:0, and anteiso-17:0. Breast milk BCFAs as a percent of total fatty acids (g per 100 g, %) were significantly different across lactation stages, with the highest concentration in colostrum, followed by transitional and mature breast milk (median: 0.41, 0.31, and 0.28%, respectively, p < 0.05). Lower BCFAs in preterm breast milk compared to term breast milk may have been related to maternal intake, or the ability of the mammary gland to extract BCFA from plasma, or differences in mammary gland BCFA synthesis. BCFAs were mainly in the sn-2 position (52-65%), similar to palmitic acid. Overall, preterm and term breast milk BCFAs were similar and showed specific concentration patterns, resembling 16:0 with respect to sn-2 positional distribution. BCFAs were reduced with lactation stage, similar to highly unsaturated fatty acids.
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Affiliation(s)
- Liang Jie
- State Key Laboratory of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, Jiangsu, PR China.
| | - Ce Qi
- State Key Laboratory of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, Jiangsu, PR China.
| | - Jin Sun
- State Key Laboratory of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, Jiangsu, PR China.
| | - Renqiang Yu
- Wuxi Maternal and Child Health Hospital, Wuxi 214002, Jiangsu, China
| | - Xiangyu Wang
- Center of Applied Processing Technology, COFCO Nutrition & Health Research Institute, Beijing 100000, PR China
| | - Sameh A Korma
- State Key Laboratory of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, Jiangsu, PR China.
| | - Jingying Xiang
- Wuxi Maternal and Child Health Hospital, Wuxi 214002, Jiangsu, China
| | - Qingzhe Jin
- State Key Laboratory of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, Jiangsu, PR China.
| | - Casimir C Akoh
- Department of Food Science and Technology, University of Georgia, Athens, GA 30602, USA
| | - Hang Xiao
- Department of Food Science and Technology, University of Massachusetts, Amherst, Massachusetts 01003, USA
| | - Xingguo Wang
- State Key Laboratory of Food Science and Technology, Synergetic Innovation Center of Food Safety and Nutrition, Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province, School of Food Science and Technology, Jiangnan University, 1800 Lihu Road, Wuxi 214122, Jiangsu, PR China.
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Zouboulis CC, Beutler C, Merk HF, Baron JM. RIS-1/psoriasin expression in epithelial skin cells indicates their selective role in innate immunity and in inflammatory skin diseases including acne. DERMATO-ENDOCRINOLOGY 2018; 9:e1338993. [PMID: 29484089 PMCID: PMC5821165 DOI: 10.1080/19381980.2017.1338993] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Accepted: 06/02/2017] [Indexed: 02/07/2023]
Abstract
Objective: RIS-1/psoriasin/S100A7 is an epithelial antimicrobial peptide, whose expression is upregulated in inflammatory skin diseases and is induced by retinoids. Its molecular expression was investigated in skin cell cultures and in skin specimens to better understand its role in inflammatory procedures of the pilosebaceous unit. Methods: rtPCR and northern blotting of RIS-1/psoriasin and the retinoid-metabolizing genes CYP26AI and CRABP-II were performed in cells cultures (keratinocytes, sebocytes, fibroblasts, endothelial cells, melanocytes, lymphocytes and prostate cells; native and treated with retinoids) and in situ hybridization in normal and inflamed skin (acne, psoriasis). Results: a) RIS-1/psoriasin is expressed in keratinocytes and fibroblasts in vitro and in keratinocytes of the stratum granulosum in vivo. Retinoids in vitro and inflammatory conditions in vivo increase the levels of RIS-1/psoriasin in keratinocytes (both), sebocytes (inflammation only) and fibroblasts (retinoids). Sebocytes and fibroblasts are the metabolically most active skin cells, since they can upregulate the expression of CRABP-II and CYP26AI, genes responsible for retinoid metabolism. Inflammation modifies the compartmentation of RIS-1/psoriasin in sebaceous glands and the follicular root sheaths. Conclusion: The present data indicate that anti-inflammatory treatment targeting the epithelial compartments of the skin, including such with antibacterial peptides, may be promising for inflammatory skin diseases.
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Affiliation(s)
- Christos C Zouboulis
- Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Merdical School Theodore Fontane, Dessau, Germany
| | - Claudia Beutler
- Julius Wolff Institute for Biomechanics and Musculosceletal Regeneration, Charité Universitaesmedizin Berlin, Berlin, Germany
| | - Hans F Merk
- Department of Dermatology and Allergology, RWTH Aachen University, Aachen, Germany
| | - Jens M Baron
- Department of Dermatology and Allergology, RWTH Aachen University, Aachen, Germany
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Svensson D, Aidoukovitch A, Anders E, Agerberth B, Andersson F, Ekblad E, Ericson D, Nebel D, Voss U, Nilsson BO. The host defense peptide LL-37 is detected in human parotid and submandibular/sublingual saliva and expressed in glandular neutrophils. Eur J Oral Sci 2018; 126:93-100. [PMID: 29424090 DOI: 10.1111/eos.12407] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
The human host defense peptide, LL-37, is an important player in the first line of defense against invading microorganisms. LL-37 and its precursor, hCAP18, have been detected in unstimulated whole saliva but no reports showing hCAP18/LL-37 in isolated, parotid, and/or submandibular/sublingual saliva have been presented. Here, we measured the levels of hCAP18/LL-37 in human parotid and submandibular/sublingual saliva and investigated the expression of hCAP18/LL-37 in parotid and submandibular gland tissue. Parotid and submandibular/sublingual saliva was collected from healthy volunteers, and the levels of hCAP18/LL-37 in saliva were analyzed by dot blot, ELISA, and western blotting. Cellular expression of hCAP18/LL-37 in human parotid and submandibular glands was investigated by immunohistochemistry. Immunoreactivity for hCAP18/LL-37 was detected in both parotid and submandibular/sublingual saliva of all individuals. The concentration of hCAP18/LL-37 was similar in parotid and submandibular/sublingual saliva, and was determined by densitometric scanning of each dot and normalization to the total protein concentration of each sample, and by ELISA. Double immunohistochemistry revealed that intravascular neutrophils of both parotid and submandibular glands express hCAP18/LL-37. For the first time, we demonstrate hCAP18/LL-37 in isolated human parotid and submandibular/sublingual saliva and expression of hCAP18/LL-37 in glandular intravascular neutrophils, indicating that neutrophils of the major salivary glands contribute to the LL-37 content of whole saliva.
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Affiliation(s)
- Daniel Svensson
- Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Alexandra Aidoukovitch
- Department of Experimental Medical Science, Lund University, Lund, Sweden.,Folktandvården Skåne, Malmö, Sweden
| | - Emma Anders
- Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Birgitta Agerberth
- Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Huddinge, Sweden
| | - Fredrik Andersson
- Regional Laboratories Region Skåne, Department of Pathology, Skåne University Hospital Lund, Lund, Sweden
| | - Eva Ekblad
- Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Dan Ericson
- Department of Cariology, Faculty of Odontology, Malmö University, Malmö, Sweden
| | - Daniel Nebel
- Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Ulrikke Voss
- Department of Experimental Medical Science, Lund University, Lund, Sweden
| | - Bengt-Olof Nilsson
- Department of Experimental Medical Science, Lund University, Lund, Sweden
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Strunk T, Hibbert J, Doherty D, Granland C, Trend S, Simmer K, Burgner D, Patole S, Currie A. Probiotics and antimicrobial protein and peptide levels in preterm infants. Acta Paediatr 2017; 106:1747-1753. [PMID: 28294428 DOI: 10.1111/apa.13826] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 02/22/2017] [Accepted: 03/07/2017] [Indexed: 12/26/2022]
Abstract
AIM To characterise the secreted and inducible antimicrobial protein and peptide (APP) levels in a prospective cohort of preterm infants (<30 weeks gestational age) with or without Bifidobacterium breve M16V supplementation during the first month of life. METHODS We analysed serial biosamples of infants who did (n = 13) or did not receive (n = 62) B. breve (3 × 109 cfu/day). Peripheral blood was obtained on days 1, 14 and 28, and infant stool prior to commencement of probiotic supplementation and on day 21. Levels of APP (bactericidal/permeability inducing protein (BPI), beta defensins 1 and 2, lactoferrin, human cathelicidin, secretory phospholipase A2) in plasma and stool were determined. Further, we characterised induced APP levels in whole blood cultured with live S. epidermidis or with agonists of Toll-like receptors 2/6 and 4. RESULTS Stool, plasma and stimulated blood APP levels changed significantly during the first month of life. Supplementation with B. breve did not affect basal or stimulated APP levels except for a transient increase in inducible BPI. CONCLUSION Supplementation with B. breve does not appear to act via modulation of systemic or enteric APP expression in preterm infants although small effects cannot be excluded. Further work with other probiotic preparations is warranted.
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Affiliation(s)
- Tobias Strunk
- Centre for Neonatal Research and Education; School of Paediatrics and Child Health; University of Western Australia; Perth WA Australia
- Neonatal Clinical Care Unit; King Edward Memorial Hospital; Perth WA Australia
| | - Julie Hibbert
- Centre for Neonatal Research and Education; School of Paediatrics and Child Health; University of Western Australia; Perth WA Australia
| | - Dorota Doherty
- School of Women's and Infant's Health; University of Western Australia; Perth WA Australia
| | - Caitlyn Granland
- Centre for Neonatal Research and Education; School of Paediatrics and Child Health; University of Western Australia; Perth WA Australia
| | - Stephanie Trend
- Centre for Neonatal Research and Education; School of Paediatrics and Child Health; University of Western Australia; Perth WA Australia
| | - Karen Simmer
- Centre for Neonatal Research and Education; School of Paediatrics and Child Health; University of Western Australia; Perth WA Australia
- Neonatal Clinical Care Unit; King Edward Memorial Hospital; Perth WA Australia
| | - David Burgner
- Murdoch Childrens Research Institute; Royal Children's Hospital; Parkville VIC Australia
- Department of Paediatrics; University of Melbourne; Melbourne VIC Australia
| | - Sanjay Patole
- Centre for Neonatal Research and Education; School of Paediatrics and Child Health; University of Western Australia; Perth WA Australia
- Neonatal Clinical Care Unit; King Edward Memorial Hospital; Perth WA Australia
| | - Andrew Currie
- Centre for Neonatal Research and Education; School of Paediatrics and Child Health; University of Western Australia; Perth WA Australia
- School of Veterinary and Life Sciences; Murdoch University; Perth WA Australia
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Yadav MK, Go YY, Kim SH, Chae SW, Song JJ. Antimicrobial and Antibiofilm Effects of Human Amniotic/Chorionic Membrane Extract on Streptococcus pneumoniae. Front Microbiol 2017; 8:1948. [PMID: 29089928 PMCID: PMC5641382 DOI: 10.3389/fmicb.2017.01948] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Accepted: 09/22/2017] [Indexed: 01/11/2023] Open
Abstract
Background:Streptococcus pneumoniae colonize the human nasopharynx in the form of biofilms. The biofilms act as bacterial reservoirs and planktonic bacteria from these biofilms can migrate to other sterile anatomical sites to cause pneumonia, otitis media (OM), bacteremia and meningitis. Human amniotic membrane contains numerous growth factors and antimicrobial activity; however, these have not been studied in detail. In this study, we prepared amniotic membrane extract and chorionic membrane extract (AME/CME) and evaluated their antibacterial and antibiofilm activities against S. pneumoniae using an in vitro biofilm model and in vivo OM rat model. Materials and Methods: The AME/CME were prepared and protein was quantified using DCTM (detergent compatible) method. The minimum inhibitory concentrations were determined using broth dilution method, and the synergistic effect of AME/CME with Penicillin-streptomycin was detected checkerboard. The in vitro biofilm and in vivo colonization of S. pneumoniae were studied using microtiter plate assay and OM rat model, respectively. The AME/CME-treated biofilms were examined using scanning electron microscope and confocal microscopy. To examine the constituents of AME/CME, we determined the proteins and peptides of AME/CME using tandem mass tag-based quantitative mass spectrometry. Results: AME/CME treatment significantly (p < 0.05) inhibited S. pneumoniae growth in planktonic form and in biofilms. Combined application of AME/CME and Penicillin-streptomycin solution had a synergistic effect against S. pneumoniae. Biofilms grown with AME/CME were thin, scattered, and unorganized. AME/CME effectively eradicated pre-established pneumococci biofilms and has a bactericidal effect. AME treatment significantly (p < 0.05) reduced bacterial colonization in the rat middle ear. The proteomics analysis revealed that the AME/CME contains hydrolase, ribonuclease, protease, and other antimicrobial proteins and peptides. Conclusion: AME/CME inhibits S. pneumoniae growth in the planktonic and biofilm states via its antimicrobial proteins and peptides. AME/CME are non-cytotoxic, natural human product; therefore, they may be used alone or with antibiotics to treat S. pneumoniae infections.
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Affiliation(s)
- Mukesh K Yadav
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea.,Institute for Medical Device Clinical Trials, Korea University College of Medicine, Seoul, South Korea
| | - Yoon Y Go
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea
| | - Shin Hye Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea
| | - Sung-Won Chae
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea
| | - Jae-Jun Song
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, South Korea
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Protecting the Newborn and Young Infant from Infectious Diseases: Lessons from Immune Ontogeny. Immunity 2017; 46:350-363. [PMID: 28329702 DOI: 10.1016/j.immuni.2017.03.009] [Citation(s) in RCA: 298] [Impact Index Per Article: 37.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 12/20/2016] [Accepted: 03/06/2017] [Indexed: 12/14/2022]
Abstract
Infections in the first year of life are common and often severe. The newborn host demonstrates both quantitative and qualitative differences to the adult in nearly all aspects of immunity, which at least partially explain the increased susceptibility to infection. Here we discuss how differences in susceptibility to infection result not out of a state of immaturity, but rather reflect adaptation to the particular demands placed on the immune system in early life. We review the mechanisms underlying host defense in the very young, and discuss how specific developmental demands increase the risk of particular infectious diseases. In this context, we discuss how this plasticity, i.e. the capacity to adapt to demands encountered in early life, also provides the potential to leverage protection of the young against infection and disease through a number of interventions.
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Moore MC, Van De Walle A, Chang J, Juran C, McFetridge PS. Human Perinatal-Derived Biomaterials. Adv Healthc Mater 2017; 6:10.1002/adhm.201700345. [PMID: 28783879 PMCID: PMC5733692 DOI: 10.1002/adhm.201700345] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 05/30/2017] [Indexed: 12/30/2022]
Abstract
Human perinatal tissues have been used for over a century as allogeneic biomaterials. Due to their advantageous properties including angiogenecity, anti-inflammation, anti-microbial, and immune privilege, these tissues are being utilized for novel applications across wide-ranging medical disciplines. Given continued clinical success, increased adoption of perinatal tissues as a disruptive technology platform has allowed for significant penetration into the multi-billion dollar biologics market. Here, we review current progress and future applications of perinatal biomaterials, as well as associated regulatory issues.
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Affiliation(s)
- Marc C Moore
- Stephenson School of Biomedical Engineering, University of Oklahoma, 202 W. Boyd Street, Carson Engineering Center, Room 107, Norman, OK 73019, P. 405-325-2621, F 405-325-7508
| | - Aurore Van De Walle
- Laboratoire Matière et Systèmes Complexes MSC, UMR 7057, CNRS & University Paris Diderot, 75205 Paris Cedex 13, France, P. +33 (0)1 57 27 62 10, F. +33 (0)1 57 27 62 11
| | - Jerry Chang
- BioD Logics, LLC., 7740A Trinity Road, Cordova, TN 38018, P. 901-417-7868
| | - Cassandra Juran
- NASA Ames Research Center, Space Bioscience BLDG 236 MS: 236-7, Moffett Field, CA 94035, P. 650-604-6390
| | - Peter S McFetridge
- J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, JG-56 Biomedical Sciences Building, P.O. Box 116131, Gainesville, FL 32611-6131, P. 352-273-9325, F 352-273-9221
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Romero R, Erez O, Maymon E, Chaemsaithong P, Xu Z, Pacora P, Chaiworapongsa T, Done B, Hassan SS, Tarca AL. The maternal plasma proteome changes as a function of gestational age in normal pregnancy: a longitudinal study. Am J Obstet Gynecol 2017; 217:67.e1-67.e21. [PMID: 28263753 PMCID: PMC5813489 DOI: 10.1016/j.ajog.2017.02.037] [Citation(s) in RCA: 65] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Revised: 02/10/2017] [Accepted: 02/23/2017] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Pregnancy is accompanied by dramatic physiological changes in maternal plasma proteins. Characterization of the maternal plasma proteome in normal pregnancy is an essential step for understanding changes to predict pregnancy outcome. The objective of this study was to describe maternal plasma proteins that change in abundance with advancing gestational age and determine biological processes that are perturbed in normal pregnancy. STUDY DESIGN A longitudinal study included 43 normal pregnancies that had a term delivery of an infant who was appropriate for gestational age without maternal or neonatal complications. For each pregnancy, 3 to 6 maternal plasma samples (median, 5) were profiled to measure the abundance of 1125 proteins using multiplex assays. Linear mixed-effects models with polynomial splines were used to model protein abundance as a function of gestational age, and the significance of the association was inferred via likelihood ratio tests. Proteins considered to be significantly changed were defined as having the following: (1) >1.5-fold change between 8 and 40 weeks of gestation; and (2) a false discovery rate-adjusted value of P < .1. Gene ontology enrichment analysis was used to identify biological processes overrepresented among the proteins that changed with advancing gestation. RESULTS The following results were found: (1) Ten percent (112 of 1125) of the profiled proteins changed in abundance as a function of gestational age; (2) of the 1125 proteins analyzed, glypican-3, sialic acid-binding immunoglobulin-type lectin-6, placental growth factor, C-C motif-28, carbonic anhydrase 6, prolactin, interleukin-1 receptor 4, dual-specificity mitogen-activated protein kinase 4, and pregnancy-associated plasma protein-A had more than a 5-fold change in abundance across gestation (these 9 proteins are known to be involved in a wide range of both physiological and pathological processes, such as growth regulation, embryogenesis, angiogenesis immunoregulation, inflammation etc); and (3) biological processes associated with protein changes in normal pregnancy included defense response, defense response to bacteria, proteolysis, and leukocyte migration (false discovery rate, 10%). CONCLUSION The plasma proteome of normal pregnancy demonstrates dramatic changes in both the magnitude of changes and the fraction of the proteins involved. Such information is important to understand the physiology of pregnancy and the development of biomarkers to differentiate normal vs abnormal pregnancy and determine the response to interventions.
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Affiliation(s)
- Roberto Romero
- Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI.
| | - Offer Erez
- Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
| | - Eli Maymon
- Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
| | - Piya Chaemsaithong
- Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
| | - Zhonghui Xu
- Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI
| | - Percy Pacora
- Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
| | - Tinnakorn Chaiworapongsa
- Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
| | - Bogdan Done
- Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI
| | - Sonia S Hassan
- Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
| | - Adi L Tarca
- Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI.
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50
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Seliem W, Bhutta ZA, Soll R, McGuire W. Topical emollient therapy for preventing infection in preterm infants in low- or middle-income countries. Hippokratia 2017. [DOI: 10.1002/14651858.cd006666.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Wael Seliem
- Mansoura University; Department of Pediatrics; Mansoura City Egypt
| | - Zulfiqar A Bhutta
- Hospital for Sick Children; Centre for Global Child Health; Toronto ON Canada M5G A04
| | - Roger Soll
- University of Vermont Medical Center; Division of Neonatal-Perinatal Medicine; 111 Colchester Avenue Burlington Vermont USA 05401
| | - William McGuire
- Centre for Reviews and Dissemination; The University of York York Y010 5DD UK
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