title: Serotonin-Exacerbated DSS-Induced Colitis Is Associated with Increase in MMP-3 and MMP-9 Expression in the Mouse Colon.
abstract: 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.
authors.affiliation: Department of Gastroenterology and Hepatology, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, China; Department of Clinical Laboratory, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, China.
authors.forename: Menglu
authors.identifier: 0000-0002-1044-396X
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology and Hepatology, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Gastroenterology and Hepatology, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, China.
authors.forename: Pan
authors.identifier: 0000-0001-6562-5296
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology and Hepatology, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology and Hepatology, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, China.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, China.
authors.forename: Yongchao
authors.identifier: 0000-0001-9274-0812
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Gastroenterology and Hepatology, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Gastroenterology and Hepatology, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, China; Department of Cancer Genetics and Epigenetics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA.
authors.forename: Fong-Fong
authors.identifier: 0000-0002-0894-3033
authors.initials: FF
authors.lastname: Chu
authors.affiliation: Department of Gastroenterology and Hepatology, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471003, China; Department of Gastroenterology and Hepatology, Beijing Rehabilitation Hospital of Capital Medical University, 1 Gongliao Road, Shijingshan District, Beijing 100114, China.
authors.forename: Qiang
authors.identifier: 0000-0002-4159-7486
authors.initials: Q
authors.lastname: Gao
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D012701:Serotonin / Q000494:pharmacology*
chemical_list: D012701:Serotonin; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9