title: SeMet inhibits IL-1β-induced rheumatoid fibroblast-like synoviocytes proliferation and the production of inflammatory mediators.
abstract: Previous studies demonstrated that Se has anti-inflammatory activities and that it plays an important role in maintaining normal cartilage metabolism. Nevertheless, little is known about the effects of Se on the production of inflammatory mediators in rheumatoid fibroblast-like synoviocytes (FLSs). The objective of this study was to determine the effects of Se on the interleukin-1β (IL-1β)-induced proliferation of FLSs and production of matrix metalloproteinases (MMPs) and inflammatory mediators by FLSs. In this study, the proliferation of FLSs was assessed using the MTT assay after cultured with/without the presence of IL-1β and SeMet. Human FLSs were pretreated with SeMet (0.5 μM) and subsequently stimulated with IL-1β (5 ng/ml) for 24 h. Production of NO and PGE2 were evaluated by the Griess reaction and ELISA. Gene expression of MMP-3, MMP-13, iNOS, and COX-2 was measured by real-time PCR. MMP-3 and MMP-13 proteins in culture medium were determined using cytokine-specific ELISA. Western immunoblotting was used to analyze the iNOS and COX-2 protein production in the culture medium and the activity of phosphorylation of P38 MAPK pathways. We found that SeMet significantly inhibits IL-1β-induced proliferation of FLSs. SeMet also inhibited the production of PGE2 and NO induced by IL-1β. SeMet significantly decreased IL-1β-stimulated gene expression and production of MMP-3, MMP-13, iNOS, and COX-2 in human FLSs. In addition, we found SeMet partly inhibited the IL-1β-induced activation of p38 MAPK pathways. The present report is first to demonstrate that SeMet inhibits IL-1β-induced expression of MMPs and production of inflammatory factors in cultured FLSs, indicating that SeMet may be a potential agent in the treatment of rheumatoid arthritis.
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, 109 Xue Yuan Xi Road, Wenzhou 325000, China.
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Ying
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Chen
authors.forename: Shaowen
authors.initials: S
authors.lastname: Cheng
authors.forename: Zhiron
authors.initials: Z
authors.lastname: Zhao
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Guo
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.forename: Jianjun
authors.initials: J
authors.lastname: Hong
authors.forename: Lei
authors.initials: L
authors.lastname: Peng
authors.forename: Huazi
authors.initials: H
authors.lastname: Xu
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D001483:Base Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D017931:DNA Primers; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000502:physiology; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012645:Selenomethionine / Q000494:pharmacology*; D015398:Signal Transduction; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017931:DNA Primers; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D012333:RNA, Messenger; D012645:Selenomethionine; D048051:p38 Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3