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Iguratimod ameliorates inflammatory responses by modulating the Th17/Treg paradigm in dextran sulphate sodium-induced murine colitis.
Mol Immunol 2018; 93:9-19MI

Abstract

Inflammatory bowel disease (IBD) is an autoimmune disease with an abnormal and persistent immune response. Iguratimod, a novel anti-rheumatic drug, exhibits anti-inflammatory effects and regulates immune response. The role of iguratimod in intestinal mucosal inflammation and immunity has not been examined. The aim of this study was to investigate whether iguratimod ameliorates dextran sulphate sodium (DSS)-induced murine colitis and its potential regulatory mechanism. Murine colitis was induced by administering 2.5% DSS for 5days. Some mice were administered iguratimod (5, 30mg/kg) by oral gavage once daily for 7days, beginning on the day 3 after colitis induction. Our study showed that iguratimod alleviates the symptoms of colitis and suppresses intestinal tissue damage, including macroscopic and histopathological manifestations. Moreover, iguratimod reduced interleukin (IL)-6, IL-17, and tumour necrosis factor-α levels, and increased the expression levels of IL-10 and TGF-β. In addition, iguratimod downregulated the proportion of Th17 cells, the level of transcription factor retinoic acid-related orphan receptor γt (RORγt), and the phosphorylation of signal transducer and activator of transcription-3 (STAT3), and upregulated the proportion of Treg cells, the level of transcription factor forkhead box p3 (Foxp3), and the phosphorylation of STAT5 in the colonic tissues. In conclusion, iguratimod plays a protective role in mice with DSS-induced colitis via anti-inflammatory effects and regulation of Th17/Treg cells. Therefore, use of iguratimod may serve as a novel therapeutic strategy for the treatment of IBD.

Authors+Show Affiliations

Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China.Department of Gastroenterology Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China.School of Life Sciences, Peking University, Beijing 100871, PR China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Radiation Medicine, Beijing 102206, PR China.Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China.Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China.Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China.Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032, PR China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Radiation Medicine, Beijing 102206, PR China. Electronic address: tangli08@aliyun.com.Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, PR China. Electronic address: wyyyhzhiming@126.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29121519

Citation

Jiang, Xue-Pei, et al. "Iguratimod Ameliorates Inflammatory Responses By Modulating the Th17/Treg Paradigm in Dextran Sulphate Sodium-induced Murine Colitis." Molecular Immunology, vol. 93, 2018, pp. 9-19.
Jiang XP, Huang XL, Yang ZP, et al. Iguratimod ameliorates inflammatory responses by modulating the Th17/Treg paradigm in dextran sulphate sodium-induced murine colitis. Mol Immunol. 2018;93:9-19.
Jiang, X. P., Huang, X. L., Yang, Z. P., Wang, S. C., Xie, W., Miao, L., ... Huang, Z. M. (2018). Iguratimod ameliorates inflammatory responses by modulating the Th17/Treg paradigm in dextran sulphate sodium-induced murine colitis. Molecular Immunology, 93, pp. 9-19. doi:10.1016/j.molimm.2017.10.008.
Jiang XP, et al. Iguratimod Ameliorates Inflammatory Responses By Modulating the Th17/Treg Paradigm in Dextran Sulphate Sodium-induced Murine Colitis. Mol Immunol. 2018;93:9-19. PubMed PMID: 29121519.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Iguratimod ameliorates inflammatory responses by modulating the Th17/Treg paradigm in dextran sulphate sodium-induced murine colitis. AU - Jiang,Xue-Pei, AU - Huang,Xie-Lin, AU - Yang,Zao-Peng, AU - Wang,Shun-Cai, AU - Xie,Wei, AU - Miao,Lei, AU - Tang,Li, AU - Huang,Zhi-Ming, Y1 - 2017/11/06/ PY - 2017/05/10/received PY - 2017/09/16/revised PY - 2017/10/11/accepted PY - 2017/11/10/pubmed PY - 2018/1/25/medline PY - 2017/11/10/entrez KW - Iguratimod KW - Inflammatory bowel disease KW - Regulatory T cells KW - T helper 17 cells SP - 9 EP - 19 JF - Molecular immunology JO - Mol. Immunol. VL - 93 N2 - Inflammatory bowel disease (IBD) is an autoimmune disease with an abnormal and persistent immune response. Iguratimod, a novel anti-rheumatic drug, exhibits anti-inflammatory effects and regulates immune response. The role of iguratimod in intestinal mucosal inflammation and immunity has not been examined. The aim of this study was to investigate whether iguratimod ameliorates dextran sulphate sodium (DSS)-induced murine colitis and its potential regulatory mechanism. Murine colitis was induced by administering 2.5% DSS for 5days. Some mice were administered iguratimod (5, 30mg/kg) by oral gavage once daily for 7days, beginning on the day 3 after colitis induction. Our study showed that iguratimod alleviates the symptoms of colitis and suppresses intestinal tissue damage, including macroscopic and histopathological manifestations. Moreover, iguratimod reduced interleukin (IL)-6, IL-17, and tumour necrosis factor-α levels, and increased the expression levels of IL-10 and TGF-β. In addition, iguratimod downregulated the proportion of Th17 cells, the level of transcription factor retinoic acid-related orphan receptor γt (RORγt), and the phosphorylation of signal transducer and activator of transcription-3 (STAT3), and upregulated the proportion of Treg cells, the level of transcription factor forkhead box p3 (Foxp3), and the phosphorylation of STAT5 in the colonic tissues. In conclusion, iguratimod plays a protective role in mice with DSS-induced colitis via anti-inflammatory effects and regulation of Th17/Treg cells. Therefore, use of iguratimod may serve as a novel therapeutic strategy for the treatment of IBD. SN - 1872-9142 UR - https://www.unboundmedicine.com/medline/citation/29121519/Iguratimod_ameliorates_inflammatory_responses_by_modulating_the_Th17/Treg_paradigm_in_dextran_sulphate_sodium_induced_murine_colitis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-5890(17)30528-X DB - PRIME DP - Unbound Medicine ER -