Serotonin-Exacerbated DSS-Induced Colitis Is Associated with Increase in MMP-3 and MMP-9 Expression in the Mouse Colon

• Published in: Mediators of inflammation 2016-01, Vol.2016 (2016), p.1-10
• Main Authors: Gao, Qiang, Chu, Fong-Fong, Chang, Yongchao, Jiang, Yalin, Feng, Dandan, Chen, Pan, Gao, Lei, Chen, Menglu, Jin, Jianjun
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Caco-2 Cells; Clinical medicine; Colitis; Colitis - chemically induced; Colitis - metabolism; Colleges & universities; Colon; Colon - drug effects; Colon - metabolism; Cytokines; Dextran; Enzymes; Gastroenterology; Gene expression; Growth factors; Hepatology; Homeostasis; Hospitals; Humans; Immunohistochemistry; Inflammation; Inflammatory bowel disease; Laboratory animals; Male; Matrix Metalloproteinase 3 - metabolism; Matrix Metalloproteinase 9 - metabolism; Mice; Mice, Inbred C57BL; Pathogenesis; Physiology; Real-Time Polymerase Chain Reaction; RNA; Rodents; Serotonin; Serotonin - pharmacology
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2016/5359768

Background. 5-HT enhances dextran sulfate sodium- (DSS-) induced colitis and is involved in inflammatory bowel disease (IBD). Matrix metalloproteinases (MMPs) play roles in the process of intestinal inflammation. Aims. To examine whether 5-HT induces MMPs expression in mouse colon to enhance DSS-induced colitis. Materials and Methods. C57BL/6J (B6) mice were treated with either low-dose (1.0 mg/kg) or high-dose (2.0 mg/kg) 5-HT by enema, low-dose (1.0%) or high-dose (2.5%) DSS, or combined low-dose (1.0%) DSS and (1.0 mg/kg) 5-HT. Mouse colitis was analyzed. MMPs and tissue inhibitors of MMPs (TIMPs) mRNA were measured by real-time quantitative RT-PCR in mouse colon and in human Caco-2 cells and neutrophils. MMP-3 and MMP-9 protein levels were quantified from immunohistochemistry (IHC) images of mouse colons. Results. 5-HT exacerbated DSS-induced colitis, low-dose 5-HT induces both MMP-3 and MMP-9, and high-dose 5-HT only increased MMP-3 mRNA expression in mouse colon. Mouse colon MMP-3 and MMP-9 protein levels were also elevated by 5-HT treatment. The MMP-2, TIMP-1, and TIMP-2 mRNA levels were increased in the inflamed colon. 5-HT induced MMP-3 and MMP-9 mRNA expression in Caco-2 and human neutrophils, respectively, in vitro. Conclusion. 5-HT induced MMP-3 and MMP-9 expression in mouse colon; these elevated MMPs may contribute to DSS-induced colitis.