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1
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Niu Q, Zhang T, Mao R, Zhao N, Deng S. Genetic association of lipid and lipid-lowering drug target genes with atopic dermatitis: a drug target Mendelian randomization study. Sci Rep 2024; 14:18097. [PMID: 39103489 PMCID: PMC11300444 DOI: 10.1038/s41598-024-69180-2] [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: 11/10/2023] [Accepted: 08/01/2024] [Indexed: 08/07/2024] Open
Abstract
Observational studies suggest dyslipidemia as an atopic dermatitis (AD) risk factor and posit that lipid-lowering drugs may influence AD risk, but the causal link remains elusive. Mendelian randomization was applied to elucidate the causal role of serum lipids in AD and assess the therapeutic potential of lipid-lowering drug targets. Genetic variants related to serum lipid traits and lipid-lowering drug targets were sourced from the Global Lipid Genetics Consortium GWAS data. Comprehensive AD data were collated from the UK Biobank, FinnGen, and Biobank Japan. Colocalization, Summary-data-based Mendelian Randomization (SMR), and mediation analyses were utilized to validate the results and pinpoint potential mediators. Among assessed targets, only Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) was significantly linked to a reduced AD risk, corroborated across three separate AD cohorts. No association between serum lipid concentrations or other lipid-lowering drug targets and diminished AD risk was observed. Mediation analysis revealed that beta nerve growth factor (b-NGF) might mediate approximately 12.8% of PCSK9's influence on AD susceptibility. Our findings refute dyslipidemia's role in AD pathogenesis. Among explored lipid-lowering drug targets, PCSK9 stands out as a promising therapeutic agent for AD.
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Affiliation(s)
- Qinwang Niu
- Sichuan Polytechnic University, Deyang, 618000, Sichuan, China
| | - Tongtong Zhang
- Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Hospital Affiliated to Chongqing Medical University, Chengdu, 610031, Sichuan, China
| | - Rui Mao
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
| | - Nana Zhao
- Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Hospital Affiliated to Chongqing Medical University, Chengdu, 610031, Sichuan, China
| | - Sui Deng
- Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, China.
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Weihrauch T, Gray N, Wiebe D, Schmelz M, Limberg MM, Raap U. TRPV1 Channel in Human Eosinophils: Functional Expression and Inflammatory Modulation. Int J Mol Sci 2024; 25:1922. [PMID: 38339203 PMCID: PMC10856050 DOI: 10.3390/ijms25031922] [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: 12/08/2023] [Revised: 01/19/2024] [Accepted: 01/29/2024] [Indexed: 02/12/2024] Open
Abstract
The transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel expressed on sensory neurons and immune cells. We hypothesize that TRPV1 plays a role in human eosinophil function and is modulated by inflammatory conditions. TRPV1 expression on human eosinophils was examined by qPCR, flow cytometry, and immunohistochemistry, respectively. TRPV1 functionality was analyzed by investigating calcium flux, apoptosis, modulation by cytokines and acidic pH, and CD69 externalization using flow cytometry. Activation of TRPV1 induced calcium influx and prolonged survival. Although eosinophils were not directly activated by TRPV1 agonists, activation by IL-3 or GM-CSF was mainly restricted to TRPV1-positive eosinophils. TRPV1 surface content was increased by acidic pH, IL-3, IL-31, IL-33, TSLP, TNF-α, BDNF, and NGF-β. Interestingly, TRPV1 was also expressed by eosinophils located in proximity to peripheral nerves in atopic dermatitis (AD) skin. In conclusion, eosinophils express functional TRPV1 channels which are increased by extracellular acidification and AD-related cytokines. Since eosinophils also express TRPV1 in AD skin, our results indicate an important role of TRPV1 for neuroimmune interaction mechanisms in itchy, inflammatory skin diseases, like AD.
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Affiliation(s)
- Tobias Weihrauch
- Division of Experimental Allergy and Immunodermatology, Faculty of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26129 Oldenburg, Germany
| | - Natalie Gray
- Division of Experimental Allergy and Immunodermatology, Faculty of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26129 Oldenburg, Germany
- Division of Anatomy, Faculty of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26129 Oldenburg, Germany
| | - Daniela Wiebe
- Division of Experimental Allergy and Immunodermatology, Faculty of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26129 Oldenburg, Germany
| | - Martin Schmelz
- Department of Experimental Pain Research, MCTN, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany
| | - Maren M. Limberg
- Division of Experimental Allergy and Immunodermatology, Faculty of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26129 Oldenburg, Germany
| | - Ulrike Raap
- Division of Experimental Allergy and Immunodermatology, Faculty of Medicine and Health Sciences, Carl von Ossietzky University Oldenburg, 26129 Oldenburg, Germany
- Research Center for Neurosensory Science, Carl von Ossietzky University Oldenburg, 26129 Oldenburg, Germany
- University Clinic of Dermatology and Allergy, Klinikum Oldenburg, University Oldenburg, 26133 Oldenburg, Germany
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Weihrauch T, Limberg MM, Gray N, Schmelz M, Raap U. Neurotrophins: Neuroimmune Interactions in Human Atopic Diseases. Int J Mol Sci 2023; 24:ijms24076105. [PMID: 37047077 PMCID: PMC10094011 DOI: 10.3390/ijms24076105] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 03/17/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
Allergic diseases are accompanied by a variety of symptoms such as pruritus, coughing, sneezing, and watery eyes, which can result in severe physiological and even psychological impairments. The exact mechanisms of these conditions are not yet completely understood. However, recent studies demonstrated a high relevance of neurotrophins in allergic inflammation, as they induce cytokine release, mediate interaction between immune cells and neurons, and exhibit different expression levels in health and disease. In this review, we aim to give an overview of the current state of knowledge concerning the role of neurotrophins in atopic disorders such as atopic dermatitis, allergic asthma, and allergic rhinitis.
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Affiliation(s)
- Tobias Weihrauch
- Division of Experimental Allergy and Immunodermatology, Faculty of Medicine and Health Sciences, University of Oldenburg, 26129 Oldenburg, Germany
| | - Maren M Limberg
- Division of Experimental Allergy and Immunodermatology, Faculty of Medicine and Health Sciences, University of Oldenburg, 26129 Oldenburg, Germany
| | - Natalie Gray
- Division of Experimental Allergy and Immunodermatology, Faculty of Medicine and Health Sciences, University of Oldenburg, 26129 Oldenburg, Germany
| | - Martin Schmelz
- Department of Experimental Pain Research, MCTN, Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany
| | - Ulrike Raap
- Division of Experimental Allergy and Immunodermatology, Faculty of Medicine and Health Sciences, University of Oldenburg, 26129 Oldenburg, Germany
- University Clinic of Dermatology and Allergy, University of Oldenburg, 26133 Oldenburg, Germany
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4
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Kussainova A, Kassym L, Bekenova N, Akhmetova A, Glushkova N, Kussainov A, Urazalina Z, Yurkovskaya O, Smail Y, Pak L, Semenova Y. Gene polymorphisms and serum levels of BDNF and CRH in vitiligo patients. PLoS One 2022; 17:e0271719. [PMID: 35905107 PMCID: PMC9337645 DOI: 10.1371/journal.pone.0271719] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 06/28/2022] [Indexed: 11/19/2022] Open
Abstract
Background Vitiligo is one of the most common hypomelanoses, in which the destruction of functioning melanocytes causes depigmentation of the skin, hair and mucous membranes. The genes encrypting brain-derived neurotrophic factor (BDNF) and corticotropin releasing hormone (CRH) might be the conceivable contributors to the development of vitiligo. This study was aimed at investigation of the serum levels of BDNF and CRH as well as their selected single nucleotide polymorphisms (SNPs) in vitiligo patients in comparison with the healthy controls. Methods The cross-sectional study was carried out between October 2020 and June 2021 in 93 vitiligo patients (age range from 23 to 48 years) and 132 healthy controls (age range from 24 to 52 years). The psychological status of study participants was evaluated using the Generalized Anxiety Disorder-7 (GAD-7) scale. Serum levels of BDNF and CRH were measured with the help of a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kit. Genotyping for the rs11030094 polymorphism of the BDNF gene and for the rs242924 polymorphism of the corticotropin releasing hormone receptor 1 (CRH-R1) gene was performed by a real-time polymerase chain reaction (PCR). Results There was a significant relationship between the CRH-R1 rs242924 and BDNF rs11030094 polymorphisms and vitiligo. Moreover, serum levels of neurotransmitters differed significantly between vitiligo and control groups and were associated with the CRH-R1 rs242924 and BDNF rs11030094 SNPs. Conclusions Our findings demonstrated the association between CRH-R1 rs242924 and BDNF rs11030094 polymorphisms and vitiligo. Further studies need to be carried out in vitiligo patients to confirm the results observed.
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Affiliation(s)
- Assiya Kussainova
- Department of Dermatovenerology and Cosmetology, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
| | - Laura Kassym
- School of Medicine, Nazarbayev University, Nur-Sultan, Republic of Kazakhstan
- * E-mail:
| | - Nazira Bekenova
- Department of Dermatovenerology and Cosmetology, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
| | - Almira Akhmetova
- Department of Dermatovenerology and Cosmetology, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
| | - Natalya Glushkova
- Department of Epidemiology, Biostatistics & Evidence Based Medicine, Al-Farabi Kazakh National University, Almaty, Republic of Kazakhstan
| | - Almas Kussainov
- Department of Psychiatry and Narcology, NJSC "Astana Medical University", Nur-Sultan, Republic of Kazakhstan
| | - Zhanar Urazalina
- Department of Emergency Medicine, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
| | - Oxana Yurkovskaya
- Department of Personalized Medicine, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
| | - Yerbol Smail
- Department of Infectious Diseases and Immunology, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
| | - Laura Pak
- Department of Clinical Oncology and Nuclear Medicine, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
| | - Yuliya Semenova
- Department of Neurology, Ophthalmology, Otorhinolaryngology, NJSC "Semey Medical University", Semey, Republic of Kazakhstan
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5
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Chen J, Chen S, Chen J, Shen B, Jiang Z, Xu Y. Study on the Molecular Basis of Huanglian Jiedu Decoction Against Atopic Dermatitis Integrating Chemistry, Biochemistry, and Metabolomics Strategies. Front Pharmacol 2022; 12:770524. [PMID: 34970141 PMCID: PMC8712871 DOI: 10.3389/fphar.2021.770524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 11/24/2021] [Indexed: 11/27/2022] Open
Abstract
Atopic dermatitis (AD) is a common chronic relapsing skin inflammation, which severely affect the quality of life of patients. Inhibiting itching and enhancing immunity to mitigate scratching are key elements in the fight against AD. Huanglian Jiedu decoction (HLJDD) has multiple pharmacological effects in the treatment of AD. However, the effective ingredients and underlying molecular mechanisms have not yet been fully explored. Thus, this study integrates chemistry, biochemistry, and metabolomics strategies to evaluate the active substance basis of HLJDD against AD. First, HLJDD was split to five fractions (CPF, 40AEF, 90AEF, PEF and WEF) and 72 chemical components were identified. NSD (Non-similarity degree) among the different fractions showed significant chemical differences (>81%). Interleukin IL-13, IL-17A, IL-3, IL-31, IL-33, IL4, IL-5, TSLP, IgE, and histamine in the serum, and IL-4Rα, JAK1, and HRH4 levels in skin, participating in inhibiting itching and regulating immunity signaling, were found to be restored to varying degrees in AD treating with HLJDD and its fractions, especially 40AEF and CPF. Untargeted metabolomics analysis demonstrated that forty metabolites were differential metabolites in plasma between the HLJDD-treated group and the AD group, involving in histidine metabolism, arginine biosynthesis, pyrimidine metabolism, and so on. Further, targeted metabolomics analysis revealed that eleven differential metabolites, associating with physiological and biochemical indices, were significant improved in the HLJDD and its fractions groups. In conclusion, HLJDD exhibited anti-AD effects by inhibiting itching and enhancing immunity, which in turn regulating the levels of relative metabolites, and CPF and 40AEF were considered the most important components of HLJDD.
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Affiliation(s)
- Jing Chen
- Department of Pharmacy, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Lin Hai, China
| | - Saizhen Chen
- Department of Pharmacy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Jinguang Chen
- Department of Dermatology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Bixin Shen
- Department of Pharmaceutics, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Zhengli Jiang
- Department of Pharmacy, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Lin Hai, China
| | - Yubin Xu
- Department of Pharmacy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
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6
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Xu Y, Chen S, Zhang L, Chen G, Chen J. The Anti-Inflammatory and Anti-Pruritus Mechanisms of Huanglian Jiedu Decoction in the Treatment of Atopic Dermatitis. Front Pharmacol 2021; 12:735295. [PMID: 34925005 PMCID: PMC8675233 DOI: 10.3389/fphar.2021.735295] [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: 11/05/2021] [Indexed: 11/13/2022] Open
Abstract
Atopic dermatitis (AD) is a common chronic skin disease driven by a T-cell-mediated immune response, with inflammation and pruritus being its main clinical manifestations. Huanglian Jiedu decoction (HLJDT), which is an ancient Chinese medicine herbal formula derived from Wai-Tai-Mi-Yao, is a potentially effective treatment for AD. We aimed to clarify the anti-inflammatory and anti-pruritus mechanisms of HLJDT in AD treatment. We performed immunohistochemistry, Western blotting, reverse transcriptase-polymerase chain reaction, Luminex-based direct multiplex immunoassay, enzyme-linked immunosorbent assays, and flow cytometry to address the abovementioned aims. HLJDT significantly reduced clinical symptoms and ear swelling in AD-like mice by inhibiting the production of cytokines [histamine, interleukin (IL)-3, IL-4, IL-5, IL-13, IL-17A, IL-31, and IL-33], substance P (SP), transient receptor potential cation channel subfamily V member 1 (TRPV-1), and gastrin-releasing peptide (GRP). Additionally, HLJDT significantly suppressed the protein expression levels and positive cell percentage of CD28, CD80, CD86, CD207, CD326, MHCII, and OX40 in the lymphoid nodes. Moreover, HLJDT significantly suppressed mRNA and protein expression of tyrosine–protein kinase (JAK1), histamine H4 receptor, and IL-4Rα, as well as the protein expression of GRP, SP, and TRPV-1 in the root ganglion. Our findings indicate that HLJDT can treat AD by regulating the antigen presentation function of dendritic cells, weakening T-lymphocyte activation, and subsequently exerting anti-inflammatory and anti-pruritus effects.
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Affiliation(s)
- Yubin Xu
- Department of Pharmacy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Saizhen Chen
- Department of Pharmacy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Lingling Zhang
- Department of Pharmacy, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
| | - Guirong Chen
- College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Shenyang, China.,67th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, Dalian, China
| | - Jinguang Chen
- Department of Dermatology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, China
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7
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Fabrazzo M, Cipolla S, Signoriello S, Camerlengo A, Calabrese G, Giordano GM, Argenziano G, Galderisi S. A systematic review on shared biological mechanisms of depression and anxiety in comorbidity with psoriasis, atopic dermatitis, and hidradenitis suppurativa. Eur Psychiatry 2021; 64:e71. [PMID: 34819201 PMCID: PMC8668448 DOI: 10.1192/j.eurpsy.2021.2249] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Mental disorders in comorbidity with chronic skin diseases may worsen disease outcome and patients' quality of life. We hypothesized the comorbidity of depression, anxiety syndromes, or symptoms as attributable to biological mechanisms that the combined diseases share. METHODS We conducted a systematic review based on the Preferred Reporting Items for Systematic Review and Meta-Analysis statement searching into PubMed, PsycInfo, and Scopus databases. We examined the literature regarding the comorbidity of psoriasis (Ps), atopic dermatitis (AD), or hidradenitis suppurativa with depression and/or anxiety in adults ≥18 years and the hypothetical shared underlying biological mechanisms. RESULTS Sixteen studies were analyzed, mostly regarding Ps and AD. Brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling and nuclear factor kappa-light-chain-enhancer of activated B cells/p38 mitogen-activated protein kinase pathways arose as shared mechanisms in Ps animal models with depression- and/or anxiety-like behaviors. Activated microglia and neuroinflammatory responses emerged in AD depressive models. As to genetic studies, atopic-dermatitis patients with comorbid anxiety traits carried the short variant of serotonin transporter and a polymorphism of the human translocator protein gene. A GA genotype of catechol-O-methyltransferase gene was instead associated with Ps. Reduced natural killer cell activity, IL-4, serotonin serum levels, and increased plasma cortisol and IgE levels were hypothesized in comorbid depressive AD patients. In Ps patients with comorbid depression, high serum concentrations of IL-6 and IL-18, as well as IL-17A, were presumed to act as shared inflammatory mechanisms. CONCLUSIONS Further studies should investigate mental disorders and chronic skin diseases concurrently across patients' life course and identify their temporal relation and biological correlates. Future research should also identify biological characteristics of individuals at high risk of the comorbid disorders and associated complications.
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Affiliation(s)
- Michele Fabrazzo
- Department of Psychiatry, University of Campania Luigi Vanvitelli, 80138Naples, Italy
| | - Salvatore Cipolla
- Department of Psychiatry, University of Campania Luigi Vanvitelli, 80138Naples, Italy
| | - Simona Signoriello
- Medical Statistics Unit, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, 80138Naples, Italy
| | - Alessio Camerlengo
- Department of Psychiatry, University of Campania Luigi Vanvitelli, 80138Naples, Italy
| | - Giulia Calabrese
- Dermatology Unit, University of Campania Luigi Vanvitelli, 80131Naples, Italy
| | - Giulia Maria Giordano
- Department of Psychiatry, University of Campania Luigi Vanvitelli, 80138Naples, Italy
| | - Giuseppe Argenziano
- Dermatology Unit, University of Campania Luigi Vanvitelli, 80131Naples, Italy
| | - Silvana Galderisi
- Department of Psychiatry, University of Campania Luigi Vanvitelli, 80138Naples, Italy
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Aksoy H, Ergun T, Akkiprik M, Peker Eyuboglu İ, Seckin Gencosmanoglu D, Cöbek Ünalan GP, Yöney H. The impact of antipsoriatic treatment on serum pro-BDNF, BDNF levels, depression, anxiety scores, and quality of life. Dermatol Ther 2021; 34:e14872. [PMID: 33580990 DOI: 10.1111/dth.14872] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 01/19/2021] [Accepted: 02/06/2021] [Indexed: 11/28/2022]
Abstract
Depression is a comorbidity of psoriasis. Suppression of neurotrophins has been proposed to cause depression. Peripheral brain-derived neurotrophic factor (BDNF) and its precursor, pro-BDNF have been shown to be altered in depression. To compare serum pro-BDNF and BDNF levels, depression, anxiety, and quality of life (QoL) in psoriasis patients, diseased, and healthy controls, to assess impact of 12-week antipsoriatic treatment on abovementioned markers. At baseline, all groups completed Beck Depression Inventory (BDI), Spielberger State-Trait Anxiety Inventory-II (STAI-II) and DLQI; serum BDNF, proBDNF levels were measured. These were repeated after 3-months of treatment in psoriasis patients. Depression and anxiety were significantly higher, QoL was poorer in psoriasis. ProBDNF and proBDNF/BDNF ratios were not different among groups at baseline but significantly decreased after treatment in psoriasis. Depression and QoL improved significantly, BDNF and anxiety scores did not change. Altered pro-BDNF and proBDNF/BDNF ratios may have a role in depression pathogenesis in psoriasis. Antipsoriatic treatment causes improvement in depression, QoL, and reduction of proBDNF and proBDNF/BDNF ratios. Effective disease control may reverse dysregulated neurotrophin pathways and its consequences like depression.
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Affiliation(s)
- Hasan Aksoy
- Department of Dermatology, Marmara University, School of Medicine, Istanbul, Turkey
| | - Tülin Ergun
- Department of Dermatology, Marmara University, School of Medicine, Istanbul, Turkey
| | - Mustafa Akkiprik
- Department of Medical Biology and Genetics, Marmara University, School of Medicine, Istanbul, Turkey
| | - İrem Peker Eyuboglu
- Department of Medical Biology and Genetics, Marmara University, School of Medicine, Istanbul, Turkey
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9
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Jackson-Cowan L, Cole EF, Silverberg JI, Lawley LP. Childhood atopic dermatitis is associated with cognitive dysfunction: A National Health Interview Survey study from 2008 to 2018. Ann Allergy Asthma Immunol 2020; 126:661-665. [PMID: 33189871 DOI: 10.1016/j.anai.2020.11.008] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 11/03/2020] [Accepted: 11/09/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Atopic dermatitis (AD) is a common inflammatory skin disease in children and adults. Little is known regarding the association of childhood AD with cognitive dysfunction. OBJECTIVE To evaluate the association of AD and cognitive dysfunction, including memory impairment, developmental delays and attention deficit (hyperactivity) disorder in US children (age <18 years). METHODS Data was analyzed from the National Health Interview Survey 2008 to 2018, which used a multistage, clustered, cross-sectional design. RESULTS The prevalences of cognitive dysfunction, such as memory impairment (0.87% vs 0.42%), developmental delays (6.96% vs 3.87%), and attention deficit (hyperactivity) disorder (10.78% vs 8.10%), were higher in children with vs without AD. In multivariable logistic regression models adjusting for age, sex, race, region, socioeconomic factors, allergic conditions, and mental health, childhood AD was associated with higher odds of memory impairment (adjusted odds ratio [95% confidence interval]: 1.84 [1.34-2.51]), developmental delays (1.54 [1.40-1.70]), and attention deficit (hyperactivity) disorder (1.31 [1.20-1.42]) compared with children without AD. Childhood atopic disease (defined as comorbid AD, asthma, allergic rhinitis, and food allergies) further increased the prevalence of developmental delays to 13.44% (2.10 [1.20-3.70]) in boys but not in girls. CONCLUSION In a nationally representative sample of the US population, a statistically significant and positive association between childhood AD and atopic disease with cognitive dysfunction was identified (P < .001). Furthermore, a dimorphic relationship with developmental delays was identified between sexes.
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Affiliation(s)
- LaDonya Jackson-Cowan
- The Medical College of Georgia at Augusta University, Augusta University/University of Georgia Medical Partnership, Athens, Georgia.
| | - Emily F Cole
- Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia
| | - Jonathan I Silverberg
- Department of Dermatology, George Washington University School of Medicine and Health Sciences, Washington, District of Columbia
| | - Leslie P Lawley
- Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia
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10
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Neuroinflammatory Gene Expression Pattern Is Similar between Allergic Rhinitis and Atopic Dermatitis but Distinct from Atopic Asthma. BIOMED RESEARCH INTERNATIONAL 2020; 2020:7196981. [PMID: 32596360 PMCID: PMC7305544 DOI: 10.1155/2020/7196981] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 04/22/2020] [Accepted: 05/05/2020] [Indexed: 11/18/2022]
Abstract
Methods In the study, we included 86 children diagnosed with atopic asthma (n = 25), allergic rhinitis (n = 20), and atopic dermatitis (n = 20) and healthy control subjects (n = 21) of Caucasian origin from the Polish population. The blood leukocyte expression of 31 genes involved in neuroinflammatory response (neurotrophins, their receptors, neuropeptides, and histamine signaling pathway) was analysed using TaqMan low-density arrays. The relative expression of selected proteins from plasma was done using TaqMan Protein Assays. Statistical analysis was done using Statistica. Results Blood expression of 31 genes related to neuroimmune interactions showed significant increase in both allergic diseases, allergic rhinitis and atopic dermatitis, in comparison to the control group. We found 12 genes significantly increased in allergic rhinitis and 9 genes in which the expression was elevated in atopic dermatitis. Moreover, 9 genes with changed expression in atopic dermatitis overlapped with those in allergic rhinitis. Atopic asthma showed 5 genes with altered expression. The peripheral expression of neuroinflammatory genes in the human study was verified in target tissues (nasal epithelium and skin) in a rat model of allergic inflammation. Conclusions A common pattern of neuroinflammatory gene expression between allergic rhinitis and atopic dermatitis may reflect similar changes in sensory nerve function during chronic allergic inflammation.
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11
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Guseva D, Rüdrich U, Kotnik N, Gehring M, Patsinakidis N, Agelopoulos K, Ständer S, Homey B, Kapp A, Gibbs BF, Ponimaskin E, Raap U. Neuronal branching of sensory neurons is associated with BDNF-positive eosinophils in atopic dermatitis. Clin Exp Allergy 2020; 50:577-584. [PMID: 31925827 DOI: 10.1111/cea.13560] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Revised: 12/20/2019] [Accepted: 01/03/2020] [Indexed: 01/01/2023]
Abstract
BACKGROUND Pruritus is a major symptom of atopic dermatitis (AD) and is transmitted by a subpopulation of non-myelinated C-type free nerve endings in the epidermis and upper dermis. Stimulation of these nerve terminals is affected by histamine, neurotrophins and physical factors. Eosinophils of patients with AD are a source of neurotrophins, including brain-derived neurotrophic factor (BDNF), levels of which correlate with disease severity. OBJECTIVE The purpose of this study was to determine the anatomical localization of eosinophils in the skin of patients with AD with regard to peripheral nerves and to investigate whether eosinophils induce sprouting and neurite outgrowth in murine sensory neurons. METHODS Cryosections of skin derived from AD and control (NA) patients were subjected to immunofluorescence analysis with markers for eosinophils, BDNF and neuronal cells. Stimulated eosinophil supernatants were used for the treatment of cultured peripheral mouse dorsal root ganglia (DRG) neurons followed by morphometric analysis. RESULTS Dermal axon density and the proximity of eosinophils to nerve fibres were significantly higher in AD patients vs NA. Both neuronal projections and eosinophils expressed BDNF. Furthermore, activated eosinophil supernatants induced BDNF-dependent mouse DRG neuron branching. CONCLUSIONS AND CLINICAL RELEVANCE Our results indicate that BDNF-positive eosinophils are also localized in close proximity with nerve fibres in AD, suggesting a functional relationship between BDNF-expressing eosinophils and neuronal projections. These observations suggest that eosinophils may have considerable impact on pruritus by supporting sensory nerve branching.
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Affiliation(s)
- Daria Guseva
- Department of Cellular Neurophysiology, Hannover Medical School, Hannover, Germany.,Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany
| | - Urda Rüdrich
- Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany
| | - Nika Kotnik
- Division of Experimental Allergology and Immunodermatology, University of Oldenburg, Oldenburg, Germany
| | - Manuela Gehring
- Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany
| | - Nikolaos Patsinakidis
- University Clinic of Dermatology and Allergy, University of Oldenburg, Oldenburg, Germany
| | - Konstantin Agelopoulos
- Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Münster, Germany
| | - Sonja Ständer
- Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Münster, Germany
| | - Bernhard Homey
- Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany
| | - Alexander Kapp
- Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany
| | - Bernhard F Gibbs
- Division of Experimental Allergology and Immunodermatology, University of Oldenburg, Oldenburg, Germany
| | - Evgeni Ponimaskin
- Department of Cellular Neurophysiology, Hannover Medical School, Hannover, Germany.,Institute of Cytology and Genetics, Novosibirsk, Russia
| | - Ulrike Raap
- Division of Experimental Allergology and Immunodermatology, University of Oldenburg, Oldenburg, Germany.,University Clinic of Dermatology and Allergy, University of Oldenburg, Oldenburg, Germany
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12
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Yin SJ, Lee JR, Kwak H, Lee BN, Han JW, Hahn MJ, Park YD, Yang JM. Functional study of 14-3-3 protein epsilon (YWHAE) in keratinocytes: microarray integrating bioinformatics approaches. J Biomol Struct Dyn 2019; 38:2633-2649. [DOI: 10.1080/07391102.2019.1637282] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Shang-Jun Yin
- College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, People’s Republic of China
| | - Jae-Rin Lee
- Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea
| | - Hyunchang Kwak
- Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea
| | - Bit-Na Lee
- Genomic Research Center, EBIOGEN Inc, Seoul, Korea
| | - Ji-Won Han
- Genomic Research Center, EBIOGEN Inc, Seoul, Korea
| | - Myong-Joon Hahn
- Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea
| | - Yong-Doo Park
- College of Biological and Environmental Sciences, Zhejiang Wanli University, Ningbo, People’s Republic of China
- Department of Dermatology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea
- Skin Diseases Research Center, Yangtze Delta Region Institute of Tsinghua University, Jiaxing, People’s Republic of China
| | - Jun-Mo Yang
- Department of Dermatology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea
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13
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Sjahrir M, Roesyanto-Mahadi ID, Effendy E. Correlation between Serum Brain-Derived Neurotrophic Factor Level and Depression Severity in Psoriasis Vulgaris Patients. Open Access Maced J Med Sci 2019; 7:583-586. [PMID: 30894916 PMCID: PMC6420937 DOI: 10.3889/oamjms.2019.142] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2019] [Revised: 02/04/2019] [Accepted: 02/05/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Psoriasis vulgaris is a chronic inflammatory skin disorder that can lead to depression. There is a similarity in neurotrophic substance in the pathogenesis of psoriasis and depression; it's called brain-derived neurotrophic factor (BDNF). BDNF level imbalance potentially affects the severity of psoriasis and depression. AIM This study aims to know the correlation between serum BDNF level and depression severity in psoriasis vulgaris patient and also the correlation between serum BDNF level and psoriasis vulgaris severity. METHODS This is an analytical cross-sectional study that 23 psoriasis vulgaris patients participated. All participants have performed serum BDNF level examination with enzyme-linked immunosorbent assay (ELISA). Depression severity assessed with Beck depression inventory-II (BDI-II) and psoriasis severity assessed with psoriasis area and severity index. Correlation between all variables was analysed with Spearman's correlation test. RESULTS Serum BDNF level and depression severity are a strongly negative correlation in psoriasis vulgaris patients (r = -0.667 with significant value p = 0.001). There is a moderate negative correlation between serum BDNF level with psoriasis vulgaris severity (r = -0.595 with significant value p = 0.003). CONCLUSION In psoriasis vulgaris patients, a low level of serum BDNF may increase depression severity and psoriasis vulgaris severity.
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Affiliation(s)
- Muhammad Sjahrir
- Dermatology and Venereology Department, Faculty of Medicine, Universitas Sumatera Utara, Jl. Dr Mansur Kampus USU Medan 20155, Indonesia
| | - Irma Damayanti Roesyanto-Mahadi
- Dermatology and Venereology Department, Faculty of Medicine, Universitas Sumatera Utara, Jl. Dr Mansur Kampus USU Medan 20155, Indonesia
| | - Elmeida Effendy
- Psychiatry Department, Faculty of Medicine, Universitas Sumatera Utara, Jl. Dr Mansur Kampus USU Medan 20155, Indonesia
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14
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Sorour NE, Elesawy FM, Tabl HA, Ibrahim ME, Akl EM. Evaluation of serum levels of neurotrophin 4 and brain-derived nerve growth factor in uremic pruritus patients. Clin Cosmet Investig Dermatol 2019; 12:109-114. [PMID: 30799944 PMCID: PMC6371925 DOI: 10.2147/ccid.s190917] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Background Pruritus is a common symptom in end-stage renal failure. Many patients suffer from this severe distressing symptom. Although several factors have been postulated to explain uremic pruritus, there is not any conclusive evidence for one of these factors. Objectives We aimed to evaluate serum levels of brain-derived nerve growth factor (BDNF), neurotrophin-4 (NT-4), serum calcium, phosphors and parathyroid hormone in uremic patients with pruritus and without pruritus compared to control subjects. Methods One hundred twenty patients suffering from renal failure and 60 healthy subjects were included in the study. Serum BDNF and NT4 levels were determined by ELISA. The serum calcium, phosphorus, parathyroid hormone and hemoglobin were also evaluated. Results Serum BDNF was significantly higher in uremic patients with pruritus (P=0.0026) and uremic patients without pruritus (P=0.0294) than control subjects. In addition, NT-4 levels were significantly elevated in uremic patients with pruritus (P<0.0001) and uremic patients without pruritus than control subjects (P=0.0016). There was no significant difference of serum level of BDNF between uremic patients with pruritus and uremic patients without pruritus (P=0.1215). However, serum NT-4 was higher in uremic patients with pruritus vs nonpruritic uremic patients with a significant difference (P=0.0026). There was a positive significant correlation between serum level of NT-4 and severity of pruritus (P=0.024). Conclusion The present study shows that NT-4 level is increased in the serum of uremic patients with pruritus and there was a significant correlation between NT-4 and severity of pruritus suggesting that NT-4 may have a role in uremic pruritus.
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Affiliation(s)
- Neveen E Sorour
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Benha University, Benha, Egypt,
| | - Fatma M Elesawy
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Benha University, Benha, Egypt,
| | - Hala A Tabl
- Department of Microbiology and Immunology, Faculty of Medicine, Benha University, Benha, Egypt
| | - Mohammed E Ibrahim
- Department of Internal Medicine, Faculty of Medicine, Benha University, Benha, Egypt
| | - Essam M Akl
- Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Benha University, Benha, Egypt,
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15
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Julio TA, Vernal S, Massaro JD, Silva MC, Donadi EA, Moriguti JC, Roselino AM. Biological predictors shared by dementia and bullous pemphigoid patients point out a cross-antigenicity between BP180/BP230 brain and skin isoforms. Immunol Res 2018; 66:567-576. [PMID: 30220011 DOI: 10.1007/s12026-018-9028-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Bullous pemphigoid (BP) following dementia diagnosis has been reported in the elderly. Skin and brain tissues express BP180 and BP230 isoforms. Dementia has been associated with rs6265 (Val66Met) polymorphism of the brain-derived neurotrophic factor (BDNF) gene and low serum BDNF. Here we investigated a possible cross-antigenicity between BP180/BP230 brain and skin isoforms. We assessed antibodies against BP180/BP230 and BDNF levels by ELISA and BDNF Val66Met SNP by PCR in three groups: 50 BP patients, 50 patients with dementia, and 50 elderly controls. Heatmap hierarchical clustering and data mining decision tree were used to analyze the patients' demographic and laboratorial data as predictors of dementia-BP association. Sixteen percent of BP patients with the lowest serological BDNF presented dementia-BP clinical association. Anti-BP180/230 positivity was unexpected observed among dementia patients (10%, 10%) and controls (14%, 1%). Indirect immunofluorescence using healthy human skin showed a BP pattern in two of 10 samples containing antibodies against BP180/BP230 obtained from dementia group but not in the control samples. Neither allelic nor genotypic BDNF Val66Met SNP was associated with dementia or with BP (associated or not with clinical manifestation of dementia). Heatmap analysis was able to differentiate the three studied groups and confirmed the ELISA results. The comprehensive data mining analysis revealed that BP patients and dementia patients shared biological predictors that justified the dementia-BP association. Autoantibodies against the BP180/BP230 brain isoforms produced by dementia patients could cross-react with the BP180/BP230 skin isoforms, which could justify cases of dementia preceding the BP disease.
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Affiliation(s)
- Tamiris A Julio
- Division of Dermatology, Department of Medical Clinics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, São Paulo, 14049-900, Brazil
| | - Sebastian Vernal
- Division of Dermatology, Department of Medical Clinics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, São Paulo, 14049-900, Brazil
| | - Juliana D Massaro
- Division of Clinical Immunology, Department of Medical Clinics, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil
| | - Matheus C Silva
- Division of Clinical Immunology, Department of Medical Clinics, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil
| | - Eduardo A Donadi
- Division of Clinical Immunology, Department of Medical Clinics, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil
| | - Julio C Moriguti
- Division of Gerontology, Department of Medical Clinics, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto, Brazil
| | - Ana M Roselino
- Division of Dermatology, Department of Medical Clinics, Ribeirão Preto Medical School, University of São Paulo, Av. Bandeirantes, 3900, Ribeirao Preto, São Paulo, 14049-900, Brazil.
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16
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Meyer NH, Gibbs B, Schmelz M, Homey B, Raap U. [Neurophysiology of atopic pruritus]. Hautarzt 2018; 69:204-209. [PMID: 29396640 DOI: 10.1007/s00105-018-4128-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Pruritus is one of the major symptoms of inflammatory skin diseases and strongly affects the quality of life in patients. Although the perception of pruritus and pain are closely intertwined, pruritus represents a distinct sensation, which is also significantly different to pain at a neurophysiological level. The pathophysiological basis of chronic and acute pruritus is not fully understood. Besides histamine, a plethora of different neuromediators of itch, including neurotrophins, neuropeptides and their corresponding receptors, have been identified. In atopic dermatitis the release of these mediators leads to an activation of immune cells, such as mast cells and eosinophilic granulocytes, which in turn release neuromediators and cytokines that activate peripheral neurons. This review focuses on the neurophysiological interactions which regulate pruritus and summarizes the function of neurological and inflammatory mediators in atopic pruritus.
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Affiliation(s)
- N H Meyer
- Department für Humanmedizin, Universitätsklinik für Dermatologie und Allergie, Universität Oldenburg, Rahel-Straus-Str. 10, 26133, Oldenburg, Deutschland
| | - B Gibbs
- Department für Humanmedizin, Universitätsklinik für Dermatologie und Allergie, Universität Oldenburg, Rahel-Straus-Str. 10, 26133, Oldenburg, Deutschland
| | - M Schmelz
- Experimentelle Schmerzforschung, Medizinische Fakultät Mannheim, Universität Heidelberg, Heidelberg, Deutschland
| | - B Homey
- Dept. für Dermatologie und Allergologie, Universität Düsseldorf, Düsseldorf, Deutschland
| | - U Raap
- Department für Humanmedizin, Universitätsklinik für Dermatologie und Allergie, Universität Oldenburg, Rahel-Straus-Str. 10, 26133, Oldenburg, Deutschland.
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17
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Hon KL, Kung JSC, Tsang KYC, Yu JWS, Cheng NS, Leung TF. Do we need another symptom score for childhood eczema? J DERMATOL TREAT 2018; 29:510-514. [DOI: 10.1080/09546634.2017.1373734] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Affiliation(s)
- Kam Lun Hon
- Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Jeng Sum Charmaine Kung
- Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Kathy Yin Ching Tsang
- Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Jasmine Wai Sum Yu
- Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Nam Sze Cheng
- Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
| | - Ting Fan Leung
- Department of Paediatrics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
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18
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Vinnik T, Kirby M, Bairachnaya M, Koman I, Tarkina T, Sadykova G, Abildinova G, Batpenova G, Pinhasov A. Seasonality and BDNF polymorphism influences depression outcome in patients with atopic dermatitis and psoriasis. World J Biol Psychiatry 2017; 18:604-614. [PMID: 27409526 DOI: 10.1080/15622975.2016.1212171] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
OBJECTIVES To examine the effect of seasonality and rs6265 genotype on depression outcome and brain-derived neurotrophic factor (BDNF) level with dermatitis patients from onset through remission. METHODS Atopic dermatitis (AD, 56) and psoriasis (PS, 33) patients and healthy controls (HC, 49) were recruited over the 2014 calendar year. Patients were subdivided by immunoglobulin E (IgE) sensitivity (AD only), season and rs6265 genotype. Assessments were performed at onset and week 10 (Hamilton Depression Rating Scale [HAM-D], SCORAD/PASI, IgE, BDNF). Patients received standard corticosteroid and antihistamine interventions. RESULTS All patients responded to corticosteroid treatment. Seasonally differential outcomes were observed in all groups. HAM-D was elevated at onset and improved over 10 weeks: AD cohort 1 (autumn/winter, AD-1) patients improved and AD cohort 2 (spring/summer, AD-2) patients remained elevated. BDNF levels were elevated in AD and seasonal differential: AD-2 declined at 10 weeks, whereas AD-1 remained high (intrinsic AD) or elevated further (extrinsic AD). PS cohort 2 declined to below control at 10 weeks. AD Val/Val had persistently elevated HAM-D and AD Val/Met were either normal (AD-1) or persistently elevated (AD-2). CONCLUSIONS Findings presented here suggest a strong influence of seasonality on depression outcome and BDNF expression in AD and PS and likely reflect separate patient populations which differentially respond to environment-based stressors.
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Affiliation(s)
- Tatyana Vinnik
- a Department of Dermatovenereology , Astana Medical University , Astana , Kazakhstan
| | - Michael Kirby
- b Department of Molecular Biology , Ariel University , Ariel , Israel
| | | | - Igor Koman
- b Department of Molecular Biology , Ariel University , Ariel , Israel
| | - Tatyana Tarkina
- a Department of Dermatovenereology , Astana Medical University , Astana , Kazakhstan
| | - Gulnaz Sadykova
- a Department of Dermatovenereology , Astana Medical University , Astana , Kazakhstan
| | - Gulshara Abildinova
- c National Research Centre of Maternal and Child Health , Astana , Kazakhstan
| | - Gulnara Batpenova
- a Department of Dermatovenereology , Astana Medical University , Astana , Kazakhstan
| | - Albert Pinhasov
- b Department of Molecular Biology , Ariel University , Ariel , Israel
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19
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Brain-derived neurotrophic factor is increased in serum levels of patients with symptomatic dermographism. Postepy Dermatol Alergol 2017; 34:346-349. [PMID: 28951710 PMCID: PMC5560183 DOI: 10.5114/ada.2017.69315] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2016] [Accepted: 06/01/2016] [Indexed: 11/17/2022] Open
Abstract
Introduction Symptomatic dermographism (SD) is the most common form of physical urticaria. However, the role of neuroimmune mechanisms in SD is unclear. Aim To investigate circulating levels of brain-derived neurotrophic factor (BDNF) in symptomatic dermographism. Material and methods Thirty-two patients suffering from SD and 33 healthy subjects were included in the study. Serum BDNF levels were determined by a human enzyme-linked immunoassay (ELISA) kit. The serum C-reactive protein concentration and eosinophil counts in peripheral blood were evaluated. Results The BDNF serum levels were detectable in both SD patients and healthy controls. The BDNF serum levels were significantly higher in patients with SD compared with healthy controls (p = 0.004). There was a positive but weak correlation between serum BDNF and CRP levels; it was not statistically significant (r = 0.211, p = 0.255). There was also a positive but weak correlation between serum BDNF and eosinophil counts; it was not statistically significant (r = 0.271, p = 0.141). Conclusions The present study shows that BDNF is increased in the serum levels of patients with SD, suggesting a role for BDNF in the pathophysiology of this disorder.
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20
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Manti S, Brown P, Perez MK, Piedimonte G. The Role of Neurotrophins in Inflammation and Allergy. VITAMINS AND HORMONES 2016; 104:313-341. [PMID: 28215300 DOI: 10.1016/bs.vh.2016.10.010] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Allergic inflammation is the result of a specific pattern of cellular and humoral responses leading to the activation of the innate and adaptive immune system, which, in turn, results in physiological and structural changes affecting target tissues such as the airways and the skin. Eosinophil activation and the production of soluble mediators such as IgE antibodies are pivotal features in the pathophysiology of allergic diseases. In the past few years, however, convincing evidence has shown that neurons and other neurosensory structures are not only a target of the inflammatory process but also participate in the regulation of immune responses by actively releasing soluble mediators. The main products of these activated sensory neurons are a family of protein growth factors called neurotrophins. They were first isolated in the central nervous system and identified as important factors for the survival and differentiation of neurons during fetal and postnatal development as well as neuronal maintenance later in life. Four members of this family have been identified and well defined: nerve growth factor, brain-derived neurotrophic factor, neurotrophin 3, and neurotrophin 4/5. Neurotrophins play a critical role in the bidirectional signaling mechanisms between immune cells and the neurosensory network structures in the airways and the skin. Pruritus and airway hyperresponsiveness, two major features of atopic dermatitis and asthma, respectively, are associated with the disruption of the neurosensory network activities. In this chapter, we provide a comprehensive description of the neuroimmune interactions underlying the pathophysiological mechanisms of allergic and inflammatory diseases.
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Affiliation(s)
- S Manti
- Center for Pediatric Research, Cleveland Clinic Foundation, Cleveland, OH, United States
| | - P Brown
- Center for Pediatric Research, Cleveland Clinic Foundation, Cleveland, OH, United States
| | - M K Perez
- Center for Pediatric Research, Cleveland Clinic Foundation, Cleveland, OH, United States; Pediatric Institute and Children's Hospital, Cleveland Clinic Foundation, Cleveland, OH, United States
| | - G Piedimonte
- Center for Pediatric Research, Cleveland Clinic Foundation, Cleveland, OH, United States; Pediatric Institute and Children's Hospital, Cleveland Clinic Foundation, Cleveland, OH, United States.
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21
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Fölster-Holst R, Papakonstantinou E, Rüdrich U, Buchner M, Pite H, Gehring M, Kapp A, Weidinger S, Raap U. Childhood atopic dermatitis-Brain-derived neurotrophic factor correlates with serum eosinophil cationic protein and disease severity. Allergy 2016; 71:1062-5. [PMID: 27087278 DOI: 10.1111/all.12916] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/12/2016] [Indexed: 01/22/2023]
Abstract
Several studies have shown that neurotrophins including brain-derived neurotrophic factor (BDNF) play a role in chronic inflammatory skin diseases such as atopic dermatitis (AD). BDNF is increased in the serum samples of adults with AD. Interestingly, eosinophils of these patients can release and produce BDNF. We analyzed BDNF serum levels with ELISA and their correlation with SCORAD score, eosinophil cationic protein (ECP), total IgE, IL-4, IL-13 and IL-31 in children with AD (n = 56) compared to nonatopic healthy children (n = 25). In addition, we analyzed FLG loss-of-function mutations in 17 children with AD and their connection to BDNF. BDNF serum levels were significantly higher in children with AD. Further, BDNF correlated with disease activity, serum ECP, and total IgE serum levels in AD. There was no difference in BDNF levels of filaggrin-positive or filaggrin-negative children with AD, and there was no correlation of BDNF with IL-31 and Th2 cytokines including IL-4 and IL-13. Together, our data add new insights into the pathophysiology of AD, suggesting that serum BDNF which correlates with disease severity contributes to the regulation of inflammation in an eosinophil-, but not Th2-dependent manner.
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Affiliation(s)
- R. Fölster-Holst
- Department of Dermatology, Venerology and Allergy; University of Kiel; Kiel Germany
| | - E. Papakonstantinou
- Department of Dermatology and Allergy; Hannover Medical School; Hannover Germany
| | - U. Rüdrich
- Department of Dermatology and Allergy; Hannover Medical School; Hannover Germany
| | - M. Buchner
- Department of Dermatology, Venerology and Allergy; University of Kiel; Kiel Germany
| | - H. Pite
- Allergy Center; CUF Descobertas Hospital and CUF Infante Santo Hospital; Lisbon Portugal
| | - M. Gehring
- Department of Dermatology and Allergy; Hannover Medical School; Hannover Germany
| | - A. Kapp
- Department of Dermatology and Allergy; Hannover Medical School; Hannover Germany
| | - S. Weidinger
- Department of Dermatology, Venerology and Allergy; University of Kiel; Kiel Germany
| | - U. Raap
- Department of Dermatology and Allergy; Hannover Medical School; Hannover Germany
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Raap U, Papakonstantinou E, Metz M, Lippert U, Schmelz M. Aktuelles zur kutanen Neurobiologie von Pruritus. Hautarzt 2016; 67:595-600. [DOI: 10.1007/s00105-016-3838-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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23
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Panek M, Jonakowski M, Zioło J, Pietras T, Wieteska Ł, Małachowska B, Mokros Ł, Szemraj J, Kuna P. Identification of Relationships Between Interleukin 15 mRNA and Brain-Derived Neurotrophic Factor II mRNA Levels With Formal Components of Temperament in Asthmatic Patients. Mol Neurobiol 2016; 54:1733-1744. [PMID: 26874516 DOI: 10.1007/s12035-016-9768-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2015] [Accepted: 02/01/2016] [Indexed: 11/30/2022]
Abstract
Asthma is a chronic inflammatory and heterogeneous disease developing mostly through allergic inflammation, which modifies the expression of various cytokines and neurotrophins. Previous studies suggest the involvement of interleukin (IL)-15 in the regulation of immune response in asthma. Brain-derived neurotrophic factor (BDNF) II plays an important role as a regulator of development and survival of neurons as well as maintenance of their physiological activity. Chronic stress associated with asthma and elevated IL-15 mRNA and BDNFII mRNA levels may affect the mood and a subjective sensation of dyspnoea-inducing anxiety. Psychopathological variables and numerous cytokine/neurotrophin interactions influence the formation of temperament and strategies of coping with stress. The aim of the study was to identify the role of IL-15 mRNA and BDNFII mRNA expressions and their effect on components of temperament and strategies of coping with stress in asthmatics. A total of 352 subjects (176 healthy volunteers and 176 asthmatic patients) participated in the study. The Formal Characteristic of Behaviour-Temperament Inventory (FCB-TI), Coping Inventory for Stressful Situations (CISS), Beck Depression Inventory, State-Trait Anxiety Inventory, and Borg Rating of Perceived Exertion (RPE) Scale were applied in all the subjects. The expression of IL-15 and BDNFII gene was measured using quantitative real-time polymerase chain reaction (qRT-PCR). Different levels of IL-15 and BDNFII expressions between healthy volunteers and patients were revealed in the study. IL-15 enhanced the BDNFII mRNA expression among patients with bronchial asthma. The depression level negatively correlated with the BDNFII mRNA expression. This neurotrophin modified the temperament variable. BDNFII significantly affected (proportional relationship) the level of briskness in asthmatic patients. BDNFII might influence the level and style of coping with stress (emotion-oriented style). This hypothesis requires further studies on protein functional models. The obtained data confirms the role of IL-15 and BDNFII in the pathomechanisms of depression and formation of selected traits defining the temperament in asthmatics.
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Affiliation(s)
- Michał Panek
- Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, 22 Kopcinskiego St., 90-153, Lodz, Poland.
| | - Mateusz Jonakowski
- Students Research Group at the Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, 22 Kopcinskiego St., 90-153, Lodz, Poland
| | - Jan Zioło
- Students Research Group at the Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, 22 Kopcinskiego St., 90-153, Lodz, Poland
| | - Tadeusz Pietras
- Department of Pneumology and Allergology, Medical University of Lodz, 22 Kopcinskiego St., 90-153, Lodz, Poland
| | - Łukasz Wieteska
- Department of Medical Biochemistry, Medical University of Lodz, 6/8 Mazowiecka St., 92-215, Lodz, Poland
| | - Beata Małachowska
- Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 36/50 Sporna St., 91-738, Lodz, Poland
| | - Łukasz Mokros
- Students Research Group at the Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, 22 Kopcinskiego St., 90-153, Lodz, Poland.,Department of Pneumology and Allergology, Medical University of Lodz, 22 Kopcinskiego St., 90-153, Lodz, Poland
| | - Janusz Szemraj
- Department of Medical Biochemistry, Medical University of Lodz, 6/8 Mazowiecka St., 92-215, Lodz, Poland
| | - Piotr Kuna
- Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, 22 Kopcinskiego St., 90-153, Lodz, Poland
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İsmi O, Özcan C, Karabacak T, Polat G, Vayisoğlu Y, Güçlütürk T, Görür K. Local Effect of Neurotrophin-3 in Neuronal Inflammation of Allergic Rhinitis: Preliminary Report. Balkan Med J 2015; 32:364-370. [PMID: 26740895 PMCID: PMC4692335 DOI: 10.5152/balkanmedj.2015.151028] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2014] [Accepted: 04/22/2015] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Allergic rhinitis is a common inflammatory nasal mucosal disease characterized by sneezing, watery nasal discharge, nasal obstruction and itching. Although allergen-specific antibodies play a main role in the allergic airway inflammation, neuronal inflammation may also contribute to the symptoms of allergic rhinitis. Neuronal inflammation is primarily caused by the stimulation of sensory nerve endings with histamine. It has been shown that neurotrophins may also have a role in allergic reactions and neuronal inflammation. Nerve growth factor, neurotrophin 3 (NT-3), neurotrophin 4/5 and brain-derived neurotrophic factor are members of the neurotrophin family. Although nerve growth factor and brain-derived neurotrophic factor are well studied in allergic rhinitis patients, the exact role of Neurotrophin-3 is not known. AIMS To investigate the possible roles of neurotrophin-3 in allergic rhinitis patients. STUDY DESIGN Case-control study. METHODS Neurotrophin-3 levels were studied in the inferior turbinate and serum samples of 20 allergic rhinitis and 13 control patients. Neurotrophin-3 staining of nasal tissues was evaluated by immunohistochemistry and ELISA was used for the determination of serum Neurotrophin-3 levels. RESULTS Neurotrophin-3 staining scores were statistically higher in the study group than in the control patients (p=0.001). Regarding serum Neurotrophin-3 levels, no statistically significant difference could be determined between allergic rhinitis and control patients (p=0.156). When comparing the serum NT-3 levels with tissue staining scores, there were no statistically significant differences in the allergic rhinitis and control groups (p=0.254 for allergic rhinitis and p=0.624 for control groups). CONCLUSION We suggest that Neurotrophin-3 might affect the nasal mucosa locally without being released into the systemic circulation in allergic rhinitis patients.
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Affiliation(s)
- Onur İsmi
- Department of Otorhinolaryngology, Mersin University Faculty of Medicine, Mersin, Turkey
| | - Cengiz Özcan
- Department of Otorhinolaryngology, Mersin University Faculty of Medicine, Mersin, Turkey
| | - Tuba Karabacak
- Department of Pathology, Mersin University Faculty of Medicine, Mersin, Turkey
| | - Gürbüz Polat
- Department of Medical Biochemistry, Mersin University Faculty of Medicine, Mersin, Turkey
| | - Yusuf Vayisoğlu
- Department of Otorhinolaryngology, Mersin University Faculty of Medicine, Mersin, Turkey
| | - Taylan Güçlütürk
- Department of Otorhinolaryngology, Gaziantep State Hospital, Gaziantep, Turkey
| | - Kemal Görür
- Department of Otorhinolaryngology, Mersin University Faculty of Medicine, Mersin, Turkey
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Brunoni AR, Lotufo PA, Sabbag C, Goulart AC, Santos IS, Benseñor IM. Decreased brain-derived neurotrophic factor plasma levels in psoriasis patients. ACTA ACUST UNITED AC 2015. [PMID: 26200230 PMCID: PMC4541690 DOI: 10.1590/1414-431x20154574] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Brain-derived neurotrophic factor (BDNF) is associated with neuroplasticity and
synaptic strength, and is decreased in conditions associated with chronic stress.
Nevertheless, BDNF has not yet been investigated in psoriasis, a chronic inflammatory
systemic disease that is exacerbated by stress. Therefore, our aim was to determine
BDNF plasma levels in psoriasis patients and healthy controls. Adult patients (n=94)
presenting with psoriasis for at least 1 year were enrolled, and age- and
gender-matched with healthy controls (n=307) from the Brazilian Longitudinal Study of
Adult Health (ELSA-Brasil). Participants had neither a previous history of coronary
artery disease nor current episode of major depression. BDNF plasma levels were
determined using the Promega ELISA kit. A general linear model was used to compare
BDNF levels in psoriasis patients and controls, with age, gender, systolic blood
pressure, serum fasting glucose, blood lipid levels, triglycerides, smoking status,
and body mass index examined. After adjusting for clinical and demographic variables,
significantly decreased BNDF plasma levels were observed in psoriasis patients
(P=0.01) (estimated marginal means of 3922 pg/mL; 95%CI=2660-5135) compared with
controls (5788 pg/mL; 95%CI=5185-6442). Similar BDNF levels were found in both mild
and severe cases of psoriasis. Our finding, that BDNF is decreased in psoriasis,
supports the concept of a brain-skin connection in psoriasis. Further studies should
determine if BDNF is increased after specific psoriasis treatments, and associated
with different disease stages.
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Affiliation(s)
- A R Brunoni
- Centro de Pesquisa Clínica e Epidemiológica, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brasil
| | - P A Lotufo
- Centro de Pesquisa Clínica e Epidemiológica, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brasil
| | - C Sabbag
- Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
| | - A C Goulart
- Centro de Pesquisa Clínica e Epidemiológica, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brasil
| | - I S Santos
- Centro de Pesquisa Clínica e Epidemiológica, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brasil
| | - I M Benseñor
- Centro de Pesquisa Clínica e Epidemiológica, Hospital das Clínicas, Universidade de São Paulo, São Paulo, SP, Brasil
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Cingi C, Muluk NB, Cobanoglu B, Çatli T, Dikici O. Nasobronchial interaction. World J Clin Cases 2015; 3:499-503. [PMID: 26090369 PMCID: PMC4468895 DOI: 10.12998/wjcc.v3.i6.499] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2014] [Revised: 11/25/2014] [Accepted: 03/20/2015] [Indexed: 02/05/2023] Open
Abstract
Upper and lower airways can be considered as a unified morphofunctional unit. In this paper, nasobronchial interactions are evaluated based on literature.To discuss nasobronchial interactions, literature review from PubMed since 1982 is evaluated. Data base was including the terms “nasobronchial interaction, nasal and bronchial”. Asthma and rhinosinusitis may be associated with environmental factors and immunological predisposition. Treatment of rhinosinusitis may decrease asthma exacerbations. It was concluded that “one airway, one disease”-concept may be accepted when considering naso-bronchial interaction. Asthma treatment should also mean treating the nose as good as treating patients with nasal symptoms. To reach the succesful results ıt should be associated with evaluation of lung functions.
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Eviston DP, Minasyan A, Mann KP, Campbell DE, Nanan RK. In utero Head Circumference is Associated with Childhood Allergy. Front Pediatr 2015; 3:73. [PMID: 26442233 PMCID: PMC4561811 DOI: 10.3389/fped.2015.00073] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Accepted: 08/10/2015] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Altered fetal growth is known to be associated with allergic disease. Specifically, increased head circumference at birth has been linked to asthma and elevated IgE. However, few studies have examined a link between early fetal anthropometry and allergic disease. The aim of this study was to examine head circumference at mid-gestation in children diagnosed with allergy. METHODS This was a retrospective cohort study, comprising pregnancies delivered between 10/2006 and 9/2010 at Nepean Hospital, Australia. Exclusion criteria were illegal drug use, alcohol consumption, gestation <35 weeks, and gestational hypertension. Pregnancy data were sourced from the Nepean Obstetric Database. Atopic diseases (asthma, atopic dermatitis, and IgE-mediated food allergy) were assessed by questionnaire at age 1-5 years. Infants from pregnancies with completed questionnaires, who also had a mid-gestation ultrasound scan, were included (N = 121). Multiple logistic regression techniques were used to model head circumference against the development of allergies. RESULTS Smaller head circumference at mid-gestation was associated with increased odds of allergic disease in children aged 1-5 years. A 1 mm smaller head circumference was associated with a 7% increased chance of allergies being later diagnosed, adjusted for gestation (95% CI: 1-14%, p = 0.036). Head circumference at mid-gestation was also inversely correlated with the presence of multiple atopic disease. CONCLUSION Smaller mid-gestational head circumference is associated with early childhood allergic disease, which suggests that fetal programing of allergic disease occurs before mid-gestation. This suggests that mediators such as brain-derived neurotrophic factor may be dysregulated early in utero in a milieu, which also predisposes to atopic disease.
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Affiliation(s)
- David P Eviston
- Discipline of Obstetrics, Gynaecology and Neonatology, Charles Perkins Centre Nepean, Sydney Medical School Nepean, The University of Sydney , Penrith, NSW , Australia
| | - Anna Minasyan
- Discipline of Paediatrics and Child Health, Charles Perkins Centre Nepean, Sydney Medical School Nepean, The University of Sydney , Penrith, NSW , Australia
| | - Kristy P Mann
- NHMRC Clinical Trials Centre, The University of Sydney , Camperdown, NSW , Australia
| | - Dianne E Campbell
- Department of Allergy and Immunology, The Children's Hospital at Westmead, The University of Sydney , Westmeabd, NSW , Australia ; Discipline of Paediatrics and Child Health, The University of Sydney , Penrith, NSW , Australia
| | - Ralph K Nanan
- Discipline of Obstetrics, Gynaecology and Neonatology, Charles Perkins Centre Nepean, Sydney Medical School Nepean, The University of Sydney , Penrith, NSW , Australia ; Discipline of Paediatrics and Child Health, The University of Sydney , Penrith, NSW , Australia
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Lee J, Park CO, Lee KH. Specific immunotherapy in atopic dermatitis. ALLERGY, ASTHMA & IMMUNOLOGY RESEARCH 2014; 7:221-9. [PMID: 25749758 PMCID: PMC4397361 DOI: 10.4168/aair.2015.7.3.221] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/03/2014] [Revised: 04/30/2014] [Accepted: 06/30/2014] [Indexed: 11/20/2022]
Abstract
Allergen specific immunotherapy (SIT) using house dust mite (HDM) extracts has been performed mainly with patients of asthma and allergic rhinitis. In the meanwhile, there has been a long debate on the efficacy of SIT in atopic dermatitis (AD) with only a few double-blind placebo-controlled trials. However, several randomized controlled trials of SIT in AD revealed significant improvement of clinical symptoms and also, positive result was shown by a following meta-analysis study of these trials. In order to predict and evaluate the treatment outcome, finding a biomarker that can predict treatment responses and treatment end-points is critical but it is very challenging at the same time due to the complexity of causes and mechanisms of AD. Other considerations including standardization of the easiest and safest treatment protocol and optimizing the treatment preparations should be studied as well. This review summarizes the basics of SIT in AD including the brief mechanisms, treatment methods and schedules, and also highlights the clinical efficacy of SIT in AD along with mild, controllable adverse reactions. Immunologic effects and studies of various biomarkers are also introduced and finally, future considerations with upcoming studies on SIT were discussed.
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Affiliation(s)
- Jungsoo Lee
- Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Chang Ook Park
- Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea
| | - Kwang Hoon Lee
- Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
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Receptors, cells and circuits involved in pruritus of systemic disorders. Biochim Biophys Acta Mol Basis Dis 2014; 1842:869-92. [DOI: 10.1016/j.bbadis.2014.02.007] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 02/16/2014] [Accepted: 02/18/2014] [Indexed: 12/12/2022]
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Yanik ME, Erfan G, Albayrak Y, Aydin M, Kulac M, Kuloglu M. Reduced serum brain-derived neurotrophic factor in patients with first onset vitiligo. Neuropsychiatr Dis Treat 2014; 10:2361-7. [PMID: 25540586 PMCID: PMC4270357 DOI: 10.2147/ndt.s74826] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Vitiligo is an acquired pigmentary skin disease that can cause serious cosmetic problems. There have been numerous and well established studies that have demonstrated the comorbidity of various psychiatric disorders in patients with vitiligo. However, to our knowledge, there have been no studies investigating whether a psychiatric biomarker, such as brain-derived neurotrophic factor (BDNF), is associated with vitiligo. PATIENTS AND METHODS This study was conducted in Namık Kemal University Medical Faculty, Departments of Dermatology and Psychiatry between January 2013 and September 2014. After meeting inclusion and exclusion criteria, serum BDNF levels were assayed in 57 patients with first onset vitiligo and no known current or past psychiatric disorder and compared with BDNF levels in 58 age and sex matched healthy subjects. RESULTS The age and female/male ratios were similar between groups. The mean values of serum BDNF were 1.57±0.97 ng/dL and 2.37±1.73 ng/dL in the vitiligo group and in the healthy control group, respectively. The mean BDNF level was significantly higher in the healthy control group compared with the vitiligo group (t=2.76, P=0.007). CONCLUSION This is the first study to compare serum BDNF levels between patients with vitiligo and healthy subjects. The reduced level of serum BDNF in patients with vitiligo may be directly related to the etiology of vitiligo or associated with the high percentage of psychiatric disorders in that patient population. Further studies are needed to support our preliminary results.
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Affiliation(s)
- M Emin Yanik
- Department of Dermatology, Faculty of Medicine, Namık Kemal University, Tekirdag, Turkey
| | - Gamze Erfan
- Department of Dermatology, Faculty of Medicine, Namık Kemal University, Tekirdag, Turkey
| | - Yakup Albayrak
- Department of Psychiatry, Faculty of Medicine, Namık Kemal University, Tekirdag, Turkey
| | - Murat Aydin
- Department of Biochemistry, Faculty of Medicine, Namık Kemal University, Tekirdag, Turkey
| | - Mustafa Kulac
- Department of Dermatology, Faculty of Medicine, Namık Kemal University, Tekirdag, Turkey
| | - Murat Kuloglu
- Department of Psychiatry, Faculty of Medicine, Akdeniz University, Antalya, Turkey
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Eichenfield LF, Tom WL, Chamlin SL, Feldman SR, Hanifin JM, Simpson EL, Berger TG, Bergman JN, Cohen DE, Cooper KD, Cordoro KM, Davis DM, Krol A, Margolis DJ, Paller AS, Schwarzenberger K, Silverman RA, Williams HC, Elmets CA, Block J, Harrod CG, Smith Begolka W, Sidbury R. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am Acad Dermatol 2013; 70:338-51. [PMID: 24290431 DOI: 10.1016/j.jaad.2013.10.010] [Citation(s) in RCA: 785] [Impact Index Per Article: 65.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2013] [Revised: 10/03/2013] [Accepted: 10/05/2013] [Indexed: 10/26/2022]
Abstract
Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in the management and care of AD, providing updated and expanded recommendations based on the available evidence. In this first of 4 sections, methods for the diagnosis and monitoring of disease, outcomes measures for assessment, and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed.
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Affiliation(s)
- Lawrence F Eichenfield
- Division of Pediatric and Adolescent Dermatology, Rady Children's Hospital San Diego, San Diego, California
| | - Wynnis L Tom
- Division of Pediatric and Adolescent Dermatology, Rady Children's Hospital San Diego, San Diego, California
| | - Sarah L Chamlin
- Department of Dermatology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois
| | - Steven R Feldman
- Department of Dermatology, Wake Forest University Health Sciences, Winston-Salem, North Carolina
| | - Jon M Hanifin
- Department of Dermatology, Oregon Health and Science University, Portland, Oregon
| | - Eric L Simpson
- Department of Dermatology, Oregon Health and Science University, Portland, Oregon
| | - Timothy G Berger
- Department of Dermatology, University of California San Francisco, San Francisco, California
| | - James N Bergman
- Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada
| | - David E Cohen
- Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, New York
| | - Kevin D Cooper
- Department of Dermatology, Case Western University, Cleveland, Ohio
| | - Kelly M Cordoro
- Department of Dermatology, University of California San Francisco, San Francisco, California
| | - Dawn M Davis
- Department of Dermatology, Mayo Clinic, Rochester, Minnesota
| | - Alfons Krol
- Department of Dermatology, Oregon Health and Science University, Portland, Oregon
| | - David J Margolis
- Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
| | - Amy S Paller
- Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | | | | | - Hywel C Williams
- Centre of Evidence-Based Dermatology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
| | - Craig A Elmets
- Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama
| | - Julie Block
- National Eczema Association, San Rafael, California
| | | | | | - Robert Sidbury
- Department of Dermatology, Seattle Children's Hospital, Seattle, Washington
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Neurogenic markers of the inflammatory process in atopic dermatitis: relation to the severity and pruritus. Postepy Dermatol Alergol 2013; 30:286-92. [PMID: 24353488 PMCID: PMC3858656 DOI: 10.5114/pdia.2013.38357] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2013] [Revised: 07/21/2013] [Accepted: 08/20/2013] [Indexed: 11/25/2022] Open
Abstract
Introduction Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease, characterized by eczematous skin lesions and intensive pruritus. Recent studies have shed light on the role of the nervous system in the pathogenesis of AD. It can influence the course of the disease through an altered pattern of cutaneous innervation and abnormal expression of neuropeptides in the lesional skin. Aim The aim of the study was to evaluate plasma concentrations of the nerve growth factor (NGF), substance P (SP) and vasoactive intestinal peptide (VIP) in AD patients in comparison to two control groups (healthy volunteers and patients suffering from psoriasis). Correlations between plasma levels of evaluated parameters, severity of the disease and selected clinical parameters (skin prick tests, total and antigen specific IgE levels) were also analysed. Material and methods Seventy-five patients with AD, 40 patients with psoriasis and 40 healthy volunteers were included into the study. Patients with AD included 52 persons suffering from an extrinsic and 23 from an intrinsic type of the disease. The severity of skin lesions was assessed with SCORAD index. Pruritus was evaluated on the basis of the questionnaire assessing the extent, frequency and intensity of pruritus. Commercial enzyme-linked immunosorbent assays (SP, NGF: R&D Systems; and VIP: Phoenix Pharmaceuticals) were used to assess the neuropeptide and NGF plasma levels. Results Nerve growth factor and VIP plasma concentrations were significantly higher in AD patients compared to psoriatic patients and healthy subjects. Substance P plasma concentrations were elevated in the extrinsic type of AD and psoriasis comparing to healthy volunteers. There were no statistically significant differences in NGF, SP and VIP plasma concentrations between the extrinsic and intrinsic type of AD. There was also no correlation between plasma levels of evaluated parameters (NGF, SP, VIP) and SCORAD index in both types of AD. However, plasma SP concentration correlated with intensity of pruritus in AD patients. Plasma VIP concentrations correlated with intensity of pruritus in the intrinsic type of AD and with IgE-mediated sensitization to moulds in the extrinsic type of disease. Conclusions Our findings confirm that NGF and VIP play a prominent role in atopic inflammatory reactions and may serve as good alternative biomarkers of AD. The results of this study also suggest a similar important role of neuroimmune interactions in both variants of AD. Increased SP plasma concentrations in both AD and psoriasis point to its possible role in modulating immune-mediated inflammation in different chronic inflammatory skin diseases. Moreover, SP and VIP seem to influence the course of AD by increasing pruritus, whereas an elevated plasma VIP level in AD patients may be related to a risk of developing IgE-mediated sensitization to certain airborne allergens.
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Narbutt J, Olejniczak I, Sobolewska-Sztychny D, Sysa-Jedrzejowska A, Słowik-Kwiatkowska I, Hawro T, Lesiak A. Narrow band ultraviolet B irradiations cause alteration in interleukin-31 serum level in psoriatic patients. Arch Dermatol Res 2012; 305:191-5. [PMID: 23108364 PMCID: PMC3606511 DOI: 10.1007/s00403-012-1293-6] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2012] [Revised: 09/30/2012] [Accepted: 10/09/2012] [Indexed: 12/31/2022]
Abstract
Scientific communications indicate the disturbed expression of neuropeptides in the skin and serum in psoriasis vulgaris (PsV) patients. Narrow-band ultraviolet radiation (NB-UVB) is one of the systemic therapies of PsV. The aim of the study was to evaluate the influence of NB-UVB therapy on substance P (SP), calcitonin gene-related peptide (CGRP), brain-derived neurotrophic factor (BDNF), corticotropin-releasing factor (CRF) and interleukin-31 (IL-31) serum concentrations in PsV patients. 59 psoriatic patients with mean PASI (psoriasis area and severity index) 14.3 were treated with NB-UVB (20 exposures). The control group consisted of 50 healthy subjects, whose age and sex matched. In all patients, serum concentration of BDNF, CRF, IL-31 substance P and CGRP was analyzed by ELISA before the treatment and in psoriatic group the analysis was also done after 10 and 20 irradiations. In patients there was found a significantly higher concentration of IL-31 (215.3 vs. 748.6 ng/ml; p < 0.0001), SP (25.7 vs. 67.2 pg/ml; p < 0.01), CGRP (31.4 vs. 44.15 pg/ml; p < 0.01) and a lower concentration of CRF (0.89 vs. 0.426 ng/ml; p < 0.0001) and BDNF (16.39 vs. 14.15 ng/ml; p = 0.1216) in comparison with the controls. 20 NB-UVB exposures caused a significant decrease in IL-31 level (748.6 vs. 631.7 ng/ml; p < 0.0001). The NB-UVB therapy had no major effect on neuropeptides serum levels regardless of a number of irradiations. On the basis of our study it can be suggested that IL-31 is involved in pathogenesis of psoriasis and the NB-UVB therapy causes alterations in its level.
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Affiliation(s)
- Joanna Narbutt
- Department of Dermatology, Medical University of Lodz, 5 Krzemieniecka, 94-017 Lodz, Poland
| | - Irmina Olejniczak
- Department of Dermatology, Medical University of Lodz, 5 Krzemieniecka, 94-017 Lodz, Poland
| | | | - Anna Sysa-Jedrzejowska
- Department of Dermatology, Medical University of Lodz, 5 Krzemieniecka, 94-017 Lodz, Poland
| | | | - Tomasz Hawro
- Department of Dermatology, Medical University of Lodz, 5 Krzemieniecka, 94-017 Lodz, Poland
| | - Aleksandra Lesiak
- Department of Dermatology, Medical University of Lodz, 5 Krzemieniecka, 94-017 Lodz, Poland
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Kabashima-Kubo R, Nakamura M, Sakabe JI, Sugita K, Hino R, Mori T, Kobayashi M, Bito T, Kabashima K, Ogasawara K, Nomura Y, Nomura T, Akiyama M, Shimizu H, Tokura Y. A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: possible immunological state of the intrinsic type. J Dermatol Sci 2012; 67:37-43. [PMID: 22591815 DOI: 10.1016/j.jdermsci.2012.04.004] [Citation(s) in RCA: 74] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2011] [Revised: 03/15/2012] [Accepted: 04/10/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Atopic dermatitis (AD) can be classified into the major extrinsic type with high serum IgE levels and impaired barrier, and the minor intrinsic type with normal IgE levels and unimpaired barrier. OBJECTIVE To characterize the intrinsic type of Japanese AD patients in the T helper cell polarization in relation to the barrier condition. METHODS Enrolled in this study were 21 AD patients with IgE<200kU/L (IgE-low group; 82.5±59.6kU/L) having unimpaired barrier, and 48 AD patients with IgE>500kU/L (IgE-high group; 8.050±10.400kU/L). We investigated filaggrin gene (FLG) mutations evaluated in the eight loci common to Japanese patients, circulating Th1, Th2 and Th17 cells by intracellular cytokine staining and flow cytometry, and blood levels of CCL17/TARC, IL-18, and substance P by ELISA. RESULTS The incidence of FLG mutations was significantly lower in the IgE-low group (10.5%) than the IgE-high group (44.4%) (normal individuals, 3.7%). The percentage of IFN-γ-producing Th1, but not Th2 or Th17, was significantly higher in the IgE-low than IgE-high group. Accordingly, Th2-attracting chemokine CCL17/TARC, was significantly lower in the IgE-low than the IgE-high group. There were no differences between them in serum IL-18 levels, or the plasma substance P levels or its correlation with pruritus. CONCLUSION The IgE-low group differed from the IgE-high group in that it had much less FLG mutations, increased frequency of Th1 cells, and lower levels of CCL17. In the intrinsic type, non-protein antigens capable of penetrating the unimpaired barrier may induce a Th1 eczematous response.
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Affiliation(s)
- Rieko Kabashima-Kubo
- Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan
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Papoiu AD, Wang H, Nattkemper L, Tey HL, Ishiuji Y, Chan YH, Schmelz M, Yosipovitch G. A study of serum concentrations and dermal levels of NGF in atopic dermatitis and healthy subjects. Neuropeptides 2011; 45:417-22. [PMID: 21893340 PMCID: PMC3659813 DOI: 10.1016/j.npep.2011.07.008] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2011] [Revised: 06/22/2011] [Accepted: 07/21/2011] [Indexed: 01/24/2023]
Abstract
Nerve growth factor (NGF) was reported to be increased in the serum and skin of atopic dermatitis (AD) patients, to the extent that serum nerve growth factor levels were proposed to serve as a marker of disease severity. We studied NGF levels in the serum and dermis using skin microdialysis and attempted to correlate them with disease severity. We also examined if potential differences between morning and evening levels of NGF can explain the phenomenon of nocturnal itch. In addition, neurogenic inflammation and itch were induced using histamine iontophoresis in lesional and non-lesional skin and the effect of experimental itch on dermal NGF concentration was examined. We found that systemic (serum) and eczematous skin levels of NGF in AD are significantly lower in comparison to healthy controls. Serum NGF decreases from morning to late afternoon in both groups. Interestingly, serum NGF levels were correlated to disease severity in the morning in AD, although the NGF concentration in AD were significantly lower than in the healthy group. The local itch and neurogenic inflammation induction via experimental histamine reduced local NGF levels in the eczema and non-lesional skin in atopics, but not in the healthy controls, where it was slightly increased. The higher the clinical severity of the eczema, a significantly less pronounced effect of neurogenic inflammation on the local levels of NGF was found. The availability of measurable NGF might be reduced by a higher expression of NGF receptors. The fluctuations of NGF levels during the day suggest a complex modulation of this neurotrophin, potentially linked to stress or to an altered neurophysiological mechanism.
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Affiliation(s)
- Alexandru D.P. Papoiu
- Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
| | - Hui Wang
- Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
| | - Leigh Nattkemper
- Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
- Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
| | - Hong Liang Tey
- Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
| | - Yozo Ishiuji
- Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
| | - Yiong-Huak Chan
- Biostatistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Clinical Research Centre, 10 Medical Drive, Singapore 117597, Singapore
| | - Martin Schmelz
- Department of Anesthesiology and Intensive Care Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany
| | - Gil Yosipovitch
- Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
- Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
- Department of Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
- Corresponding author at: Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. Tel.: +1 (336) 716 2901; fax: +1 (336) 716 7732. (G. Yosipovitch)
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Andiappan AK, Parate PN, Anantharaman R, Suri BK, Wang DY, Chew FT. Genetic variation in BDNF is associated with allergic asthma and allergic rhinitis in an ethnic Chinese population in Singapore. Cytokine 2011; 56:218-23. [PMID: 21723144 DOI: 10.1016/j.cyto.2011.05.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2010] [Revised: 03/30/2011] [Accepted: 05/10/2011] [Indexed: 10/18/2022]
Abstract
Allergic diseases affect more than 25% of the world population and result from a complex interplay between genetic and environmental factors. Recent evidence has shown that BDNF (Brain Derived Neurotrophic Factor) could serve as an important marker of allergic disease. Increased levels of BDNF in blood, bronchoalveolar lavage fluid and nasal lavage fluid positively correlate with disease activity and severity in patients with allergic rhinitis (AR), asthma and atopic eczema. However, reports on the association between genetic variation in BDNF and allergic disease have been controversial. This study therefore aims to clarify the relationship between single nucleotide polymorphisms (SNPs) in BDNF and a genetic predisposition to AR and asthma in an ethnic Chinese population of Singapore. Volunteers with a self-reported history of asthma (718 subjects) or a history of AR as determined by a researcher-administered questionnaire (795 subjects) were used in this study, alongside controls with no personal or family history of allergy (717 subjects). The association results identified a significant association for the tagSNP rs10767664 with a significant PDominant=0.0007 and OR=1.3 for AR and PDominant=0.0005 and OR=1.3 for asthma (using a dominant model of association). The haplotype based analysis also identified a significant association further confirming the single SNP association. The SNP rs10767664 is strongly linked (r2=0.95) to the functional polymorphism rs6265 (Val66Met), which has previously been reported to be associated to allergic phenotypes and also shown to affect BDNF expression. BDNF is a therefore a key molecular player in allergy. Further studies on polymorphisms within BDNF may shed light on its role in the pathogenesis of allergic diseases and potentially serve as biomarkers for allergic disease.
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Affiliation(s)
- Anand Kumar Andiappan
- Department of Biological Sciences, National University of Singapore, Science Drive 4, Singapore 117543, Singapore
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Rössing K, Novak N, Mommert S, Pfab F, Gehring M, Wedi B, Kapp A, Raap U. Brain-derived neurotrophic factor is increased in serum and skin levels of patients with chronic spontaneous urticaria. Clin Exp Allergy 2011; 41:1392-9. [DOI: 10.1111/j.1365-2222.2011.03795.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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Saito A, Tanaka H, Usuda H, Shibata T, Higashi S, Yamashita H, Inagaki N, Nagai H. Characterization of skin inflammation induced by repeated exposure of toluene, xylene, and formaldehyde in mice. ENVIRONMENTAL TOXICOLOGY 2011; 26:224-232. [PMID: 19904815 DOI: 10.1002/tox.20547] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Abstract
Volatile organic compounds (VOCs) are considered the main cause of sick building syndrome and they are likely to irritate the skin, eyes, and mucous membrane; however, the toxic threshold and the mechanisms of cutaneous reaction induced by long-time VOC exposure have not been clarified. In the present study, we investigated the effect of repeated painting of VOCs onto mouse skin. Various concentrations of toluene, xylene, and formaldehyde (FA) were applied once a week for 5 weeks. While FA solution (2-10%) induced remarkable ear swelling and caused evident infiltration of inflammatory cells, high concentrations of toluene and xylene (50 or 100%) evoked mild ear swelling and marginal inflammatory cell invasion. In addition, FA exposure markedly increased the expression of interleukin-4 (IL-4), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and transient receptor potential vanilloid-1 (TRPV-1) mRNAs in the ears and IL-4 and NT-3 mRNAs in the cervical lymph nodes. Furthermore, capsazepine, a TRPV-1 antagonist, significantly suppressed ear swelling caused by repeated painting of 5% FA. These findings demonstrate that FA has more potent irritancy against skin than toluene or xylene and suggest that the Th2 response, neurotrophins and TRPV-1 play important roles in FA-induced skin inflammation.
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Affiliation(s)
- Asaka Saito
- Laboratory of Pharmacology, Department of Bioactive Molecules, Gifu Pharmaceutical University, Gifu, Japan
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Abstract
PURPOSE OF REVIEW Allergic rhinitis is characterized by allergic airway inflammation and a hyperresponsiveness to nonspecific stimuli which is partly neuronally controlled. In this regard, neurotrophins are prime candidates as mediators of neuronal and immunological plasticity and they will be the focus of the current review. RECENT FINDINGS Neurotrophins including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are expressed in the nasal mucosa. The majority of NGF expression has been found in eosinophil granulocytes, the glandular apparatus and peripheral nerves. As shown recently, nasal allergen provocation upregulates BDNF expression in nasal mucosa and NGF expression on peripheral nerves and nasal lavage in patients with allergic rhinitis. In this regard, increased BDNF expression positively correlates with the maximum increase in total nasal symptom score. The neurotrophin receptors including pan-neurotrophin receptor p75, tyrosine kinase A (trkA) and trkB are expressed in nasal tissue. TrkA is expressed on endothelial, p75 on peripheral nerves and trkB on nasal mucosa mast cells that decreases after allergen provocation. The expression of these neurotrophin receptors is increased on peripheral blood eosinophils in allergic rhinitis compared with nonatopic controls. Further, BDNF and NGF exert immunomodulatory functions on eosinophils of patients with allergic rhinitis. Finally, eosinophils of patients with allergic rhinitis are capable of BDNF and NGF production. SUMMARY Neurotrophins represent prime candidates in upper airway pathophysiology in allergic rhinitis. Research on neurotrophins in allergic rhinitis is thus becoming a progressively more exciting field and may reveal new and promising therapeutic options for the future.
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Tokura Y. Extrinsic and intrinsic types of atopic dermatitis. J Dermatol Sci 2010; 58:1-7. [PMID: 20207111 DOI: 10.1016/j.jdermsci.2010.02.008] [Citation(s) in RCA: 239] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2010] [Revised: 02/08/2010] [Accepted: 02/09/2010] [Indexed: 10/19/2022]
Abstract
Atopic dermatitis (AD) can be categorized into the extrinsic and intrinsic types. Extrinsic or allergic AD shows high total serum IgE levels and the presence of specific IgE for environmental and food allergens, whereas intrinsic or non-allergic AD exhibits normal total IgE values and the absence of specific IgE. While extrinsic AD is the classical type with high prevalence, the incidence of intrinsic AD is approximately 20% with female predominance. The clinical features of intrinsic AD include relative late onset, milder severity, and Dennie-Morgan folds, but no ichthyosis vulgris or palmar hyperlinearity. The skin barrier is perturbed in the extrinsic, but not intrinsic type. Filaggrin gene mutations are not a feature of intrinsic AD. The intrinsic type is immunologically characterized by the lower expression of interleukin (IL) -4, IL-5, and IL-13, and the higher expression of interferon-gamma. It is suggested that intrinsic AD patients are not sensitized with protein allergens, which induce Th2 responses, but with other antigens, and metals might be one of the candidates of such antigens.
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Affiliation(s)
- Yoshiki Tokura
- Department of Dermatology, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
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Das UN. Obesity: genes, brain, gut, and environment. Nutrition 2009; 26:459-73. [PMID: 20022465 DOI: 10.1016/j.nut.2009.09.020] [Citation(s) in RCA: 137] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2009] [Revised: 09/21/2009] [Accepted: 09/27/2009] [Indexed: 01/04/2023]
Abstract
Obesity, which is assuming alarming proportions, has been attributed to genetic factors, hypothalamic dysfunction, and intestinal gut bacteria and an increase in the consumption of energy-dense food. Obesity predisposes to the development of type 2 diabetes mellitus, hypertension, coronary heart disease, and certain forms of cancer. Recent studies have shown that the intestinal bacteria in obese humans and mice differ from those in lean that could trigger a low-grade systemic inflammation. Consumption of a calorie-dense diet that initiates and perpetuates obesity could be due to failure of homeostatic mechanisms that regulate appetite, food consumption, and energy balance. Hypothalamic factors that regulate energy needs of the body, control appetite and satiety, and gut bacteria that participate in food digestion play a critical role in the onset of obesity. Incretins, cholecystokinin, brain-derived neurotrophic factor, leptin, long-chain fatty acid coenzyme A, endocannabinoids and vagal neurotransmitter acetylcholine play a role in the regulation of energy intake, glucose homeostasis, insulin secretion, and pathobiology of obesity and type 2 diabetes mellitus. Thus, there is a cross-talk among the gut, liver, pancreas, adipose tissue, and hypothalamus. Based on these evidences, it is clear that management of obesity needs a multifactorial approach.
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Zeilinger S, Pinto LA, Nockher WA, Depner M, Klopp N, Illig T, von Mutius E, Renz H, Kabesch M. The effect of BDNF gene variants on asthma in German children. Allergy 2009; 64:1790-4. [PMID: 19895626 DOI: 10.1111/j.1398-9995.2009.02131.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Allergic inflammation can trigger neuronal dysfunction and structural changes in the airways and the skin. Levels of brain-derived neurotrophic factor (BDNF) are strongly up regulated at the location of allergic inflammation. AIM We systematically investigated whether polymorphisms in the BDNF gene influence the development or severity of asthma and atopic diseases. METHODS The BDNF gene was screened for mutations in 80 chromosomes. Genotyping of six BDNF tagging polymorphisms was performed in a cross-sectional study population of 3099 children from Dresden and Munich (age 9-11 years, ISAAC II). Furthermore, polymorphisms were also investigated in an additional 655 asthma cases analysed with a random sample of 767 children selected from ISAAC II. Associations were calculated via chi-square test and anova using SAS Genetics and spss. RESULTS We identified nine polymorphisms with minor allele frequency >or=0.03, one of them leading to an amino acid change from Valine to Methionine. In the cross-sectional study population, no significant association was found with asthma or any atopic disease. However, when more severe asthma cases from the MAGIC study were analysed, significant asthma effects were observed with rs6265 (odds ratio 1.37, 95% confidence interval 1.14-1.64, P = 0.001), rs11030101 (OR 0.82, 95%CI 0.70-0.95, P = 0.009) and rs11030100 (OR 1.19, 95%CI 1.00-1.42, P = 0.05). CONCLUSIONS As in previous studies, effects of BDNF polymorphisms on asthma remain controversial. The data may suggest that BDNF polymorphisms contribute to severe forms of asthma.
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Affiliation(s)
- S Zeilinger
- University Children's Hospital, Ludwig Maximilian's University Munich, Germany
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Ott H, Wilke J, Baron JM, Höger PH, Fölster-Holst R. Soluble immune receptor serum levels are associated with age, but not with clinical phenotype or disease severity in childhood atopic dermatitis. J Eur Acad Dermatol Venereol 2009; 24:395-402. [PMID: 19744181 DOI: 10.1111/j.1468-3083.2009.03419.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Soluble immune receptors (SIRs) have been proposed as biomarkers in patients with atopic dermatitis (AD). However, their clinical applicability in affected children has rarely been studied. OBJECTIVE To assess the diagnostic usefulness of serum SIRs in childhood AD by correlating the obtained receptor profiles with serological parameters and clinical features such as age, AD phenotype and disease severity. METHODS We investigated 100 children with AD. The sCD14, sCD23, sCD25, sCD30, total IgE (tIgE) and eosinophilic cationic protein (ECP) were determined using sera of all children. The clinical phenotype was classified as extrinsic AD (ADe) or intrinsic AD (ADi) by the presence of allergen-specific IgE antibodies. RESULTS A total of 55 male and 45 female children were recruited. The sCD23, sCD25 and sCD30 serum levels revealed significant age-dependency. At a mean SCORAD of 40 (range 8-98), none of the evaluated SIRs was correlated to disease severity. In all, 73% of patients suffered from ADe while 27% showed the ADi phenotype. None of the analysed SIRs differed significantly between ADe and ADi patients, while tIgE and ECP levels were elevated in the ADe subgroup. CONCLUSION The current study provides evidence that sCD23, sCD25 and sCD30 serum levels are highly age-dependent. Serum concentrations of all investigated SIRs did not significantly correlate with disease severity in children with AD and were not differentially expressed in patients of different AD phenotypes. Therefore, we believe that the studied SIRs cannot be regarded as clinically useful biomarkers for the assessment of childhood AD.
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Affiliation(s)
- H Ott
- Department of Dermatology and Allergology, University Hospital Aachen, Aachen.
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Mori T, Ishida K, Mukumoto S, Yamada Y, Imokawa G, Kabashima K, Kobayashi M, Bito T, Nakamura M, Ogasawara K, Tokura Y. Comparison of skin barrier function and sensory nerve electric current perception threshold between IgE-high extrinsic and IgE-normal intrinsic types of atopic dermatitis. Br J Dermatol 2009; 162:83-90. [DOI: 10.1111/j.1365-2133.2009.09440.x] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Phillips TM, Wellner EF. Chip-based immunoaffinity CE: application to the measurement of brain-derived neurotrophic factor in skin biopsies. Electrophoresis 2009; 30:2307-12. [PMID: 19569127 PMCID: PMC2778805 DOI: 10.1002/elps.200900095] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
A chip-based immunoaffinity CE system has been employed to measure the concentrations of brain-derived neurotrophic factor in human skin biopsies, taken during atopic inflammatory events. The device employs a replaceable immunoaffinity disk to which capture antibodies have been chemically immobilized. Homogenates obtained from micro-dissected human skin samples were injected into the system, where the analyte of interest was captured in the immunoextraction port, thus allowing non-reactive materials to be removed prior to analysis. The captured analyte was labeled in situ with a red-emitting laser dye before being released from the capture antibody, separated by electrophoresis, and the resolved peaks detected by online LIF. Comparison of this chip-based system with conventional immunoassay demonstrated good correlation when analyzing both standards and patient samples. The system was semi-automated resulting in a CE analysis within 1.5 min and a total of circa 5 min. Intra- and inter-assay CV's of 3.85 and 4.19 were achieved with circa 98.8% recovery of brain-derived neurotrophic factor at a concentration of 100 pg/mL. The assay demonstrated clear differences between clinical stages of atopic dermatitis in human patients and could run 10-15 samples per hour. This system holds the potential for being modified to be a portable unit that could be used in clinics and other biomedical screening studies.
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Affiliation(s)
- Terry M Phillips
- Ultramicro Immunodiagnostics Section, Laboratory of Bioengineering and Physical Science, National Institute of Biomedical Imaging and Bioengineering, NIH, Bethesda, MD 20892, USA.
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Ma L, Gao XH, Zhao LP, Di ZH, Mchepange UO, Zhang L, Chen HD, Wei HC. Brain-derived neurotrophic factor gene polymorphisms and serum levels in Chinese atopic dermatitis patients. J Eur Acad Dermatol Venereol 2009; 23:1277-81. [PMID: 19522715 DOI: 10.1111/j.1468-3083.2009.03308.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Brain-derived neurotrophic factor (BDNF) plays an important role in the pathogenesis of atopic dermatitis (AD). Whether BDNF gene polymorphisms are associated with Chinese AD remains totally unknown. OBJECTIVE The aim is to determine if BDNF gene C270T and G196A polymorphisms are associated with Chinese AD, and analyse the clinical relevance of BDNF gene polymorphisms and BDNF serum levels. Methods We conducted a case-control association analysis (160 patients and 169 controls) in Northern Chinese subjects. Genotyping was performed by restriction fragment length polymorphism, and serum levels of BDNF were measured using enzyme-linked immunosorbent assay. RESULTS For C270T, there were significant differences in C/T genotype distribution (P = 0.003) and T allele frequencies (P = 0.004) between AD patients and controls in the whole dataset. Higher C/T genotype frequencies were found in male AD (10.6% vs. 1.1%, P = 0.018) and in intrinsic AD (IAD; 15.79% vs. 2.91%, P = 0.008). No association between G196A polymorphism and AD was observed in the whole cohort, while A allele was much more frequent in AD patients with atopy in first-degree relatives (65.8% vs. 34.2%, P = 0.038). Serum BDNF levels were correlated with IAD severity as measured by Scoring Atopic Dermatitis index (r = 0.576, P < 0.001). CONCLUSION T allele in C270T may be a risk factor for AD, especially in IAD and male AD. A allele in G196A may be a risk factor in AD patients with atopy in first-degree relatives. Serum BDNF levels were correlated with the severity of IAD.
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Affiliation(s)
- L Ma
- State Key Department of Dermatology, No.1 Hospital of China Medical University, Shenyang, China
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