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Xue Q, Pan JP, Qian D, Ji J, Fei LY, Yao S, Tan X, Fan WG. Exploring the Impact of Systemic Inflammatory Regulators on Rosacea Risk: A Bidirectional Mendelian Randomization Analysis. Clin Cosmet Investig Dermatol 2025; 18:191-200. [PMID: 39867972 PMCID: PMC11760274 DOI: 10.2147/ccid.s495773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 01/13/2025] [Indexed: 01/28/2025]
Abstract
Objective Rosacea is a common chronic inflammatory disorder primarily affecting the face. While inflammatory factors are known to play a pivotal role in its pathogenesis, their causal relationship with rosacea remains unclear. This study employed a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the causal links between systemic inflammatory regulators and rosacea. Methods Data on 41 cytokines and growth factors were analyzed from a genome-wide association study (GWAS) meta-analysis involving 8293 individuals and genetic data from the FinnGen database, comprising 1195 rosacea cases and 211,139 controls. The principal inverse variance weighting (IVW) method was used to assess causal relationships, with sensitivity analyses, including heterogeneity and horizontal pleiotropy assessments, conducted to ensure result robustness. Results MR analysis revealed that decreased expression of Stem Cell Factor (SCF), Macrophage Inflammatory Protein-1β (MIP-1β), and Monocyte Chemotactic Protein-1 (MCP-1) was associated with increased rosacea risk (OR = 1.54, 95% CI = 1.05-2.26, p = 0.026). Conversely, elevated expression levels of Stromal Cell-Derived Factor-1α (SDF-1α) and Hepatocyte Growth Factor (HGF) were linked to higher rosacea risk (OR = 1.61, 95% CI = 1.12-2.31, p = 0.009). Reverse MR analyses showed no significant impact of rosacea on systemic inflammatory regulator expression. Conclusion This study identified five inflammatory factors-SCF, SDF-1α, MCP-1, HGF, and MIP-1β-as having causal relationships with rosacea pathogenesis. Further research is required to elucidate their mechanistic roles in disease development.
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Affiliation(s)
- Qiao Xue
- Department of Dermatology, Changshu No. 1 People’s Hospital, Changshu Hospital Affiliated to Soochow University, Changshu, Jiangsu, 215500, People’s Republic of China
| | - Jian Peng Pan
- Department of Hand Surgery, Changshu No. 2 People’s Hospital, The Affiliated Changshu Hospital of Nantong University, Changshu, Jiangsu, 215500, People’s Republic of China
| | - Da Qian
- Department of Burn and Plastic Surgery-Hand Surgery, Changshu No. 1 People’s Hospital, Changshu Hospital Affiliated to Soochow University, Changshu, Jiangsu, 215500, People’s Republic of China
| | - Jie Ji
- Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210000, People’s Republic of China
| | - Lai Yi Fei
- Department of Dermatology, Changshu No. 1 People’s Hospital, Changshu Hospital Affiliated to Soochow University, Changshu, Jiangsu, 215500, People’s Republic of China
| | - Sheng Yao
- Department of Dermatology, Changshu No. 1 People’s Hospital, Changshu Hospital Affiliated to Soochow University, Changshu, Jiangsu, 215500, People’s Republic of China
| | - Xing Tan
- Department of Dermatology, Changshu No. 1 People’s Hospital, Changshu Hospital Affiliated to Soochow University, Changshu, Jiangsu, 215500, People’s Republic of China
| | - Wen Ge Fan
- Department of Dermatology, Changshu No. 1 People’s Hospital, Changshu Hospital Affiliated to Soochow University, Changshu, Jiangsu, 215500, People’s Republic of China
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Tian H, Xu W, Wen L, Song T, Tian Y, Tang L, Guo N, Chen Q, Wang H, Zhang K, Zhang X, Peng Y. Relationship between CCL2 gene 2518A/G (rs1024611) polymorphism and age-related macular degeneration susceptibility: meta-analysis and trial sequential analysis. Int Ophthalmol 2024; 44:348. [PMID: 39141020 DOI: 10.1007/s10792-024-03266-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 07/29/2024] [Indexed: 08/15/2024]
Abstract
PURPOSE This study aimed to investigate the association between the CC-cytokine ligand-2 (CCL2) 2518A/G (rs1024611) single nucleotide polymorphism (SNP) and susceptibility to age-related macular degeneration (AMD). METHODS PubMed, Embase, Web of Science, and other databases were searched for articles published before August 24, 2023. After searching, data extraction, and quality assessment, meta-analysis and trial sequential analysis were conducted using RevMan 5.4, Stata 17.0, and TSA 0.9.5.10 Beta software. Combined OR, P values, and 95% confidence intervals (CIs) were calculated. Sensitivity analysis, subgroup analysis and publication bias assessment were also performed. RESULTS Six articles, comprising 1186 cases and 1124 controls, were included. No significant statistical difference was found in six main outcomes. However, due to observed heterogeneity and high sensitivity, subgroup analysis was performed, revealing statistically significant differences across different regions. No significant publication bias was observed. Trial sequential analysis suggested the need for additional follow-up case-control studies to further validate the findings. CONCLUSION The CCL2 gene 2518A/G (rs1024611) polymorphism is associated with AMD susceptibility. Among Caucasian populations in West Asia and Europe, the G allele is protective against AMD, whereas in East and South Asia, it poses a risk factor.
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Affiliation(s)
- Haokun Tian
- Joint Programme of Nanchang University and Queen Mary University of London, Nanchang University, Nanchang, China
- Queen Mary School, Nanchang University, Nanchang, China
- Nanchang Joint Programme, School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK
| | - Weikai Xu
- Joint Programme of Nanchang University and Queen Mary University of London, Nanchang University, Nanchang, China
- Queen Mary School, Nanchang University, Nanchang, China
- Nanchang Joint Programme, School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK
| | - Lequan Wen
- Joint Programme of Nanchang University and Queen Mary University of London, Nanchang University, Nanchang, China
- Queen Mary School, Nanchang University, Nanchang, China
- Nanchang Joint Programme, School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK
| | - Tiangang Song
- Joint Programme of Nanchang University and Queen Mary University of London, Nanchang University, Nanchang, China
- Queen Mary School, Nanchang University, Nanchang, China
- Nanchang Joint Programme, School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK
| | - Ye Tian
- Joint Programme of Nanchang University and Queen Mary University of London, Nanchang University, Nanchang, China
- Queen Mary School, Nanchang University, Nanchang, China
- Nanchang Joint Programme, School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK
| | - Lirui Tang
- Joint Programme of Nanchang University and Queen Mary University of London, Nanchang University, Nanchang, China
- Queen Mary School, Nanchang University, Nanchang, China
- Nanchang Joint Programme, School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK
| | - Nan Guo
- The Third Affiliated Hospital of Nanchang University, Nanchang, China
- The Third Clinical Medical College, Nanchang University, Nanchang, China
| | - Qianxi Chen
- Joint Programme of Nanchang University and Queen Mary University of London, Nanchang University, Nanchang, China
- Queen Mary School, Nanchang University, Nanchang, China
- Nanchang Joint Programme, School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK
| | - Haoran Wang
- Joint Programme of Nanchang University and Queen Mary University of London, Nanchang University, Nanchang, China
- Queen Mary School, Nanchang University, Nanchang, China
- Nanchang Joint Programme, School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK
| | - Kaiyuan Zhang
- College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Xinyuan Zhang
- Joint Programme of Nanchang University and Queen Mary University of London, Nanchang University, Nanchang, China
- Queen Mary School, Nanchang University, Nanchang, China
- Nanchang Joint Programme, School of Biological and Behavioural Sciences, Queen Mary University of London, London, UK
| | - Yu Peng
- Department of Ophthalmology, First Affiliated Hospital of Nanchang University, Nanchang, China.
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Li L, Liu H, Yu J, Sun Z, Jiang M, Yu H, Wang C. Intestinal Microbiota and Metabolomics Reveal the Role of Auricularia delicate in Regulating Colitis-Associated Colorectal Cancer. Nutrients 2023; 15:5011. [PMID: 38068869 PMCID: PMC10708550 DOI: 10.3390/nu15235011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 12/01/2023] [Accepted: 12/02/2023] [Indexed: 12/18/2023] Open
Abstract
BACKGROUND The edible fungus Auricularia delicate (ADe) is commonly employed in traditional medicine for intestinal disorders; however, its inhibitory effect on colitis-associated colorectal cancer (CAC) and the underlying mechanisms remain unexplored. (2) Methods: The inhibitory effect of ADe on CAC was investigated using a mouse model induced by azoxymethane/dextran sulfate sodium. RESULTS ADe effectively suppressed the growth and number of intestinal tumors in mice. Intestinal microbiota analyses revealed that ADe treatment increased Akkermansia and Parabacteroides while it decreased Clostridium, Turicibacter, Oscillospira, and Desulfovibrio. ADe regulated the levels of 2'-deoxyridine, creatinine, 1-palmitoyl lysophosphatidylcholine, and choline in serum. Furthermore, the levels of these metabolites were associated with the abundance of Oscillospira and Paraacteroides. ADe up-regulated the free fatty acid receptor 2 and β-Arrestin 2, inhibited the nuclear factor kappa B (NF-κB) pathway, and significantly attenuated the levels of inflammatory cytokines, thereby mitigating the inflammatory in CAC mice. CONCLUSIONS The protective effect of ADe in CAC mice is associated with the regulation of intestinal microbiota, which leads to the inhibition of NF-kB pathway and regulation of inflammation.
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Affiliation(s)
- Lanzhou Li
- Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China; (L.L.); (J.Y.); (Z.S.)
- School of Life Sciences, Jilin University, Changchun 130012, China;
| | - Honghan Liu
- School of Life Sciences, Jilin University, Changchun 130012, China;
| | - Jinqi Yu
- Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China; (L.L.); (J.Y.); (Z.S.)
| | - Zhen Sun
- Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China; (L.L.); (J.Y.); (Z.S.)
- School of Life Sciences, Jilin University, Changchun 130012, China;
| | - Ming Jiang
- College of Life Science and Technology, Mudanjiang Normal University, Mudanjiang 157011, China;
| | - Han Yu
- College of Agriculture, Jilin Agricultural University, Changchun 130118, China
| | - Chunyue Wang
- Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun 130118, China; (L.L.); (J.Y.); (Z.S.)
- School of Life Sciences, Jilin University, Changchun 130012, China;
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Singh S, Anshita D, Ravichandiran V. MCP-1: Function, regulation, and involvement in disease. Int Immunopharmacol 2021; 101:107598. [PMID: 34233864 PMCID: PMC8135227 DOI: 10.1016/j.intimp.2021.107598] [Citation(s) in RCA: 423] [Impact Index Per Article: 105.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 02/25/2021] [Accepted: 03/17/2021] [Indexed: 02/08/2023]
Abstract
MCP-1 (Monocyte chemoattractant protein-1), also known as Chemokine (CC-motif) ligand 2 (CCL2), is from family of CC chemokines. It has a vital role in the process of inflammation, where it attracts or enhances the expression of other inflammatory factors/cells. It leads to the advancement of many disorders by this main mechanism of migration and infiltration of inflammatory cells like monocytes/macrophages and other cytokines at the site of inflammation. MCP-1 has been inculpated in the pathogenesis of numerous disease conditions either directly or indirectly like novel corona virus, cancers, neuroinflammatory diseases, rheumatoid arthritis, cardiovascular diseases. The elevated MCP-1 level has been observed in COVID-19 patients and proven to be a biomarker associated with the extremity of disease along with IP-10. This review will focus on involvement and role of MCP-1 in various pathological conditions.
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Affiliation(s)
- Sanjiv Singh
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Export Promotion Industrial Park (EPIP), Zandaha Road, Hajipur, Bihar, India.
| | - D Anshita
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Export Promotion Industrial Park (EPIP), Zandaha Road, Hajipur, Bihar, India
| | - V Ravichandiran
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Export Promotion Industrial Park (EPIP), Zandaha Road, Hajipur, Bihar, India
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Gaiani F, Rotoli BM, Ferrari F, Barilli A, Visigalli R, Carra MC, de'Angelis GL, de'Angelis N, Dall'Asta V. Monocytes from infliximab-resistant patients with Crohn's disease exhibit a disordered cytokine profile. Sci Rep 2020; 10:12238. [PMID: 32699266 PMCID: PMC7376177 DOI: 10.1038/s41598-020-68993-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 07/03/2020] [Indexed: 01/09/2023] Open
Abstract
Crohn's disease (CD) is a chronic inflammatory disorder characterized by immune response dysregulation. Tumor necrosis factor-α (TNFα) is a key cytokine in the pathogenesis of CD, as indicated by the efficacy of anti-TNF-α therapy with infliximab (IFX). However, approximately 30-40% of CD patients fail to respond to IFX with still unclear underlying mechanisms. This study compares the inflammatory phenotype of monocytes from CD patients, who respond or non-respond to IFX. Under basal conditions, the mRNA for the cytokines TNFα, IL-23, IL-1β and the chemokines CXCL8/IL-8, CCL5/RANTES and CCL2/MCP-1 was up-regulated in monocytes from non-responders than responders. The expression of the same cytokines and CCL2/MCP-1 was higher in non-responders also upon LPS treatment. Moreover, higher secretion of TNFα, IL-1β, IFNγ and IL-2 proteins occurred in the supernatants of LPS-treated non-responders cells. Resistance to IFX in CD may result from a transcriptional dysregulation of circulating monocytes, leading to hyperactivation of pro-inflammatory pathways. Monocytes' cytokine profile may thus represent a predictive marker of response to IFX. Monocytes were isolated from blood samples of 19 CD patients (11 responders, 8 non-responders) and incubated with or without LPS. Cytokine profiles were assessed by RT-qPCR and, in the supernatants, by ELISA assay.
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Affiliation(s)
- Federica Gaiani
- Gastroenterology and Endoscopy Unit, Department of Medicine and Surgery, University of Parma, University Hospital of Parma, Via Gramsci 14, 43126, Parma, Italy.
| | - Bianca Maria Rotoli
- Unit of General Pathology, Department of Medicine and Surgery, University of Parma, Via Volturno 39, 43125, Parma, Italy
| | - Francesca Ferrari
- Unit of General Pathology, Department of Medicine and Surgery, University of Parma, Via Volturno 39, 43125, Parma, Italy
| | - Amelia Barilli
- Unit of General Pathology, Department of Medicine and Surgery, University of Parma, Via Volturno 39, 43125, Parma, Italy
| | - Rossana Visigalli
- Unit of General Pathology, Department of Medicine and Surgery, University of Parma, Via Volturno 39, 43125, Parma, Italy
| | - Maria Clotilde Carra
- Rothschild Hospital, AP-HP, Université de Paris, 5 rue Santerre, 75012, Paris, France
| | - Gian Luigi de'Angelis
- Gastroenterology and Endoscopy Unit, Department of Medicine and Surgery, University of Parma, University Hospital of Parma, Via Gramsci 14, 43126, Parma, Italy
| | - Nicola de'Angelis
- Department of Digestive, Hepatobiliary Surgery and Liver Transplantation, Henri Mondor University Hospital, AP-HP, Université Paris Est-UPEC, 51 avenue du Maréchal de Lattre de Tassigny, 94010, Créteil, France
| | - Valeria Dall'Asta
- Unit of General Pathology, Department of Medicine and Surgery, University of Parma, Via Volturno 39, 43125, Parma, Italy
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Nunes NS, Kim S, Sundby M, Chandran P, Burks SR, Paz AH, Frank JA. Temporal clinical, proteomic, histological and cellular immune responses of dextran sulfate sodium-induced acute colitis. World J Gastroenterol 2018; 24:4341-4355. [PMID: 30344419 PMCID: PMC6189848 DOI: 10.3748/wjg.v24.i38.4341] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 08/06/2018] [Accepted: 08/24/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the temporal clinical, proteomic, histological and cellular immune profiles of dextran sulfate sodium (DSS)-induced acute colitis.
METHODS Acute colitis was induced in C57Bl/6 female mice by administration of 1%, 2% or 3% DSS in drinking water for 7 d. Animals were monitored daily for weight loss, stool consistency and blood in the stool, while spleens and colons were harvested on day 8. A time course analysis was performed in mice ingesting 3% DSS, which included colon proteomics through multiplex assay, colon histological scoring by a blinded investigator, and immune response through flow cytometry or immunohistochemistry of the spleen, mesenteric lymph node and colon.
RESULTS Progressive worsening of clinical colitis was observed with increasing DSS from 1% to 3%. In mice ingesting 3% DSS, colon shortening and increase in pro-inflammatory factors starting at day 3 was observed, with increased spleen weights at day 6 and day 8. This coincided with cellular infiltration in the colon from day 2 to day 8, with progressive accumulation of macrophages F4/80+, T helper CD4+ (Th), T cytotoxic CD8+ (Tcyt) and T regulatory CD25+ (Treg) cells, and progressive changes in colonic pathology including destruction of crypts, loss of goblet cells and depletion of the epithelial barrier. Starting on day 4, mesenteric lymph node and/or spleen presented with lower levels of Treg, Th and Tcyt cells, suggesting an immune cell tropism to the gut.
CONCLUSION These results demonstrate that the severity of experimental colitis is dependent on DSS concentration, correlated with clinical, proteomic, histological and cellular immune response on 3% DSS.
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Affiliation(s)
- Natalia Schneider Nunes
- Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, United States
- Gastroenterology and Hepatology Sciences Graduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-093, Brazil
| | - Saejeong Kim
- Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, United States
| | - Maggie Sundby
- Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, United States
| | - Parwathy Chandran
- Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, United States
| | - Scott Robert Burks
- Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, United States
| | - Ana Helena Paz
- Gastroenterology and Hepatology Sciences Graduate Program, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-093, Brazil
| | - Joseph Alan Frank
- Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, United States
- National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, United States
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Abstract
PURPOSE OF REVIEW Monocyte chemoattractant protein (MCP)-1, a chemokine regulating monocyte chemotaxis and T-lymphocyte differentiation by binding to the CC chemokine receptor 2 (CCR2), plays a crucial role in the pathogenesis of inflammatory diseases, atherosclerosis and cancer. This review summarizes the current knowledge on the regulation and importance of the MCP-1/CCR2 axis, focusing on the therapeutic potential of its inhibition. RECENT FINDINGS Differential modulation of MCP-1 and CCR2 lead to downstream activation pathways, pathogenetic to differing disease conditions characterized by dysregulated monocyte/macrophage tissue recruitment. Pharmacological targeting of the MCP-1/CCR2 axis has led to selective MCP-1/CCR2 antagonists that have now entered phase I/II clinical trials for the treatment of inflammatory diseases, atherosclerosis and cancer. The pleiotropic nonselective MCP-1/CCR2 inhibition by current pharmacological agents is thought to contribute to their anti-inflammatory and antiatherosclerotic effects that is also seen for nutraceutical compounds such as curcumin. SUMMARY MCP-1 has a critical role in regulating chemotaxis both in health and disease, with increasing interest in its pharmacological inhibition. However, the therapeutic efficacy and safety of targeting the MCP-1/CCR2 axis is still in evolution.
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Su N, Zhao N, Wang G, Wang L, Zhang Y, Li R, Liu Y, Yang X, Li C, Hou M. Association of MCP-1 rs1024611 polymorphism with diabetic foot ulcers. Medicine (Baltimore) 2018; 97:e11232. [PMID: 29995756 PMCID: PMC6076038 DOI: 10.1097/md.0000000000011232] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Monocyte chemotactant protein-1 (MCP-1), a pro-inflammatory cytokine, plays an important role in inflammatory process. In present study, we evaluated the association of MCP-1 gene rs1024611 polymorphism with risk and clinical characteristics of diabetic foot ulcers (DFUs).This study recruited 116 patients with DFUs, 135 patients with diabetes mellitus (DM) without complications (non-DFU), and 149 healthy controls (HCs). MCP-1 gene rs1024611 polymorphism was genotyped by direct sequencing. The expression of MCP-1 was analyzed using quantitative real-time polymerase chain reaction. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assume the association strength.Individuals with rs1024611 AG and GG genotypes exhibited significantly higher susceptibility to DFUs, in the comparison with HCs (AG vs AA, OR = 2.364, 95% CI = 1.021-5.470; GG vs AA, OR = 2.686, 95% CI = 1.154-6.255). Meanwhile, G allele was associated with increased DFUs susceptibility (OR = 1.457, 95% CI = 1.014-2.093). Besides, rs1024611 SNP was slightly correlated with increased DFUs susceptibility in patients with DM. GG genotype of rs1024611 was significantly correlated with higher epidermal thickness and lower dermis thickness in patients with DFUs (P < .01). Patients with DFU exhibited upregulation of MCP-1 mRNA, and GG genotype was correlated with enhanced MCP-1 expression in DFU and non-DFU groups.Rs1024611 polymorphism was significantly associated with MCP-1 expression and individual susceptibility to DFUs.
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Affiliation(s)
- Na Su
- Department of Second Endocrinology
| | | | | | | | | | | | | | | | | | - Mingming Hou
- Department of Medical Records, Cangzhou Central Hospital, Cangzhou, China
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Wang Y, Liu Q, Liu T, Zheng Q, Xu X, Liu X, Gao W, Li Z, Bai X. Early plasma monocyte chemoattractant protein 1 predicts the development of sepsis in trauma patients: A prospective observational study. Medicine (Baltimore) 2018; 97:e0356. [PMID: 29620667 PMCID: PMC5902265 DOI: 10.1097/md.0000000000010356] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Monocyte chemoattractant protein 1 (MCP-1) is an initiating cytokine of the inflammatory cascade. Extracellular MCP-1 exhibits pro-inflammatory characteristic and plays a central pathogenic role in critical illness. The purpose of the study was to identify the association between plasma MCP-1 levels and the development of sepsis after severe trauma.The plasma levels of MCP-1 in severe trauma patients were measured by a quantitative enzyme-linked immune sorbent assay and the dynamic release patterns were recorded at three time points during seven days post-trauma. The related factors of prognosis were compared between sepsis and non-sepsis groups and analyzed using multivariate logistic regression analysis. We also used receiver operating characteristic (ROC) curves to assess the values of different variables in predicting sepsis.A total of 72 patients who met criteria indicative of severe trauma (72.22% of male; mean age, 49.40 ± 14.29 years) were enrolled. Plasma MCP-1 concentrations significantly increased on post-trauma day 1 and that this increase was significantly correlated with the Injury Severity Score (ISS) and interleukin-6 (IL-6). Multivariate logistic regression analysis showed that early MCP-1, ISS, and IL-6 were independent risk factors for sepsis in severe trauma patients. Incorporation of the early MCP-1 into the ISS can increase the discriminative performance for predicting development of sepsis.Early plasma MCP-1 concentrations can be used to assess the severity of trauma and is correlated with the development of sepsis after severe trauma. The addition of the early MCP-1 levels to the ISS significantly improves its ability to predict development of sepsis.
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Shen Y, Xie X, Li Z, Huang Y, Ma L, Shen X, Liu Y, Zhao Y. Interleukin-17-induced expression of monocyte chemoattractant protein-1 in cardiac myocytes requires nuclear factor κB through the phosphorylation of p65. Microbiol Immunol 2017; 61:280-286. [PMID: 28593659 DOI: 10.1111/1348-0421.12495] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2016] [Revised: 05/26/2017] [Accepted: 05/26/2017] [Indexed: 01/24/2023]
Affiliation(s)
- Yan Shen
- Department of Clinical Laboratory; The First Affiliated Hospital of Zhengzhou University; No. 1 JianShe Road Zhengzhou 450052 China
| | - Xin Xie
- Department of Clinical Laboratory; The First Affiliated Hospital of Zhengzhou University; No. 1 JianShe Road Zhengzhou 450052 China
| | - Zhuolun Li
- Department of Clinical Laboratory; The First Affiliated Hospital of Zhengzhou University; No. 1 JianShe Road Zhengzhou 450052 China
| | - Yan Huang
- Department of Clinical Laboratory; The First Affiliated Hospital of Zhengzhou University; No. 1 JianShe Road Zhengzhou 450052 China
| | - Li Ma
- Department of Clinical Laboratory; The First Affiliated Hospital of Zhengzhou University; No. 1 JianShe Road Zhengzhou 450052 China
| | - Xinhe Shen
- Department of Clinical Laboratory; The First Affiliated Hospital of Zhengzhou University; No. 1 JianShe Road Zhengzhou 450052 China
| | - Yanyue Liu
- Department of Clinical Laboratory; The First Affiliated Hospital of Zhengzhou University; No. 1 JianShe Road Zhengzhou 450052 China
| | - Yuxia Zhao
- Department of Clinical Laboratory; The First Affiliated Hospital of Zhengzhou University; No. 1 JianShe Road Zhengzhou 450052 China
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He J, Chen Y, Lin Y, Zhang W, Cai Y, Chen F, Liao Q, Yin Z, Wang Y, Tao S, Lin X, Huang P, Cui L, Shao Y. Association study of MCP-1 promoter polymorphisms with the susceptibility and progression of sepsis. PLoS One 2017; 12:e0176781. [PMID: 28472164 PMCID: PMC5417587 DOI: 10.1371/journal.pone.0176781] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2017] [Accepted: 04/17/2017] [Indexed: 12/17/2022] Open
Abstract
Previous studies have indicated that the monocyte chemo-attractant protein 1 (MCP-1), also referred to as C-C motif chemokine ligand 2 (CCL2), plays a significant role in the pathogenesis of sepsis, and this study investigated the clinical relevance of two MCP-1 gene polymorphisms on sepsis onset and progression. The Multiplex SNaPshot genotyping method was used to detect MCP-1 gene polymorphisms in the Chinese Han population (403 sepsis patients and 400 controls). MCP-1 mRNA expression levels were measured using real-time quantitative PCR, and enzyme-linked immunosorbent assays were used to analyze MCP-1, tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) and interleukin-1 beta (IL-1β) plasma concentrations. The rs1024611 polymorphism analysis showed lower frequencies of minor homozygous genotype (AA) and allele (A) in sepsis patients compared to the healthy controls (19.4% vs. 31.5%, P = 0.0001 and 45.9% vs. 54.8%, P = 0.0004, respectively). And the frequencies of GG genotype and G allele were lower in sepsis patients compared to the controls (19.6% vs. 31.3%, P = 0.0002 and 46.0% vs. 54.5%, P = 0.0007, respectively). The rs1024611 AG/GG and rs2857656 GC/CC genotypes were both overrepresented in patients with severe sepsis (both P = 0.0005) and septic shock (P = 0.010 and P = 0.015, respectively) compared to the patients with mild sepsis. Moreover, among sepsis patients, the rs1024611 AG/GG and rs2857656 GC/CC carriers exhibited significant increases in expression levels of MCP-1 (P = 0.025), TNF-α (P = 0.034) and IL-6 (P = 0.043) compared with the rs1024611 AA or rs2857656 GG carriers. This study provides valuable clinical evidence that the MCP-1/CCL2 polymorphisms rs1024611 and rs2857656 are associated with sepsis susceptibility and development. We conclude that MCP-1/CCL2 plays a significant role in the pathogenesis of sepsis, which has potentially important therapeutic implications.
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Affiliation(s)
- Junbing He
- The Intensive Care Unit, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Yuhua Chen
- The Department of Endocrinology and Metabolism, Longgang District People's Hospital of Shenzhen, Shenzhen, Guangdong, China
| | - Yao Lin
- The Department of Stomatology, Jieyang Affiliated Hospital, SunYat-sen University, Jieyang, Guangdong, China
| | - Wenying Zhang
- The Intensive Care Unit, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Yujie Cai
- Institute of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Feng Chen
- The Intensive Care Unit, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Qinghui Liao
- The Department of Endocrinology and Metabolism, Longgang District People's Hospital of Shenzhen, Shenzhen, Guangdong, China
| | - Zihan Yin
- The Intensive Care Unit, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Yan Wang
- Institute of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Shoubao Tao
- The Intensive Care Unit, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Xiaoli Lin
- The Department of Stomatology, Jieyang Affiliated Hospital, SunYat-sen University, Jieyang, Guangdong, China
| | - Pengru Huang
- Institute of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Lili Cui
- Institute of Neurology, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
- * E-mail: (LC); (YS)
| | - Yiming Shao
- The Intensive Care Unit, Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
- * E-mail: (LC); (YS)
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Jin X, Chen D, Zheng RH, Zhang H, Chen YP, Xiang Z. miRNA-133a-UCP2 pathway regulates inflammatory bowel disease progress by influencing inflammation, oxidative stress and energy metabolism. World J Gastroenterol 2017; 23:76-86. [PMID: 28104982 PMCID: PMC5221288 DOI: 10.3748/wjg.v23.i1.76] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Revised: 10/09/2016] [Accepted: 11/16/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the role of the miR-133a-UCP2 pathway in the pathogenesis of inflammatory bowel disease (IBD) and to explore the potential downstream mechanisms with respect to inflammation, oxidative stress and energy metabolism.
METHODS C57BL/6 mice were fed dextran sulfate sodium (DSS) liquid for 7 consecutive days, followed by the administration of saline to the DSS group, UCP2 siRNA to the UCP2 group and a miR-133a mimic to the miR-133a group on days 8 and 11. Body weight, stool consistency and rectal bleeding were recorded daily, and these composed the disease activity index (DAI) score for the assessment of disease severity. After cervical dislocation was performed on day 14, the length of the colon in each mouse was measured, and colonic tissue was collected for further study, which included the following: haematoxylin and eosin staining, UCP2 and miR-133a detection by immunohistochemical staining, western blot and quantitative real-time PCR, measurement of apoptosis by TUNEL assay, and the assessment of inflammation (TNF-α, IL-1β, IL-6 and MCP1), oxidative stress (H2O2 and MDA) and metabolic parameters (ATP) by ELISA and colorimetric methods.
RESULTS An animal model of IBD was successfully established, as shown by an increased DAI score, shortened colon length and specific pathologic changes, along with significantly increased UCP2 and decreased miR-133a levels. Compared with the DSS group, the severity of IBD was alleviated in the UCP2 and the miR-133a groups after successful UCP2 knockdown and miR-133a overexpression. The extent of apoptosis, as well as the levels of TNF-α, IL-1β, MDA and ATP, were significantly increased in both the UCP2 and miR-133a groups compared with the DSS group.
CONCLUSION The miR-133a-UCP2 pathway participates in IBD by altering downstream inflammation, oxidative stress and markers of energy metabolism, which provides novel clues and potential therapeutic targets for IBD.
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Zablotna M, Sobjanek M, Purzycka-Bohdan D, Szczerkowska-Dobosz A, Nedoszytko B, Nowicki R. The -2518 A/GMCP-1and -403 G/ARANTESpromoter gene polymorphisms are associated with psoriasis vulgaris. Clin Exp Dermatol 2016; 41:878-883. [DOI: 10.1111/ced.12937] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/29/2016] [Indexed: 11/27/2022]
Affiliation(s)
- M. Zablotna
- Department of Dermatology, Venereology and Allergology; Medical University of Gdansk; Gdansk Poland
| | - M. Sobjanek
- Department of Dermatology, Venereology and Allergology; Medical University of Gdansk; Gdansk Poland
| | - D. Purzycka-Bohdan
- Department of Dermatology, Venereology and Allergology; Medical University of Gdansk; Gdansk Poland
| | - A. Szczerkowska-Dobosz
- Department of Dermatology, Venereology and Allergology; Medical University of Gdansk; Gdansk Poland
| | - B. Nedoszytko
- Department of Dermatology, Venereology and Allergology; Medical University of Gdansk; Gdansk Poland
| | - R. Nowicki
- Department of Dermatology, Venereology and Allergology; Medical University of Gdansk; Gdansk Poland
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Sambyal V, Guleria K, Kapahi R, Manjari M, Sudan M, Uppal MS, Singh NR. Association of the -2518 A/G Polymorphism of MCP-1 with Breast Cancer in Punjab, North-West India. Asian Pac J Cancer Prev 2015; 16:7243-8. [DOI: 10.7314/apjcp.2015.16.16.7243] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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