title: Cyclic mechanical stretch downregulates IL-1β-induced COX-2 expression and PGE(2) production in rheumatoid arthritis fibroblast-like synoviocytes.
abstract: In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) are one of the primary sources of inflammatory cytokines, including prostaglandins (PGs) and matrix metalloproteinases (MMPs) in joints that are detrimental to the bone, cartilage, and the surrounding tissue. Many studies, in recent years, have shown that physiotherapies play a beneficial effect on the maintenance of joint homeostasis in RA; however, the underlying mechanisms involved are still not fully elucidated. This study was performed to investigate cellular mechanism of mechanical strain-mediated actions in RA-FLS. RA-FLS were grown on collagen-coated silicone membranes and were exposed to 6% cyclic mechanical stretch at a frequency of 0.5 Hz for different times in the presence/absence of IL-1β. Real-time PCR and western blotting were used to detect the mRNA and protein level of cyclooxygenase-2 (COX-2) and MMP-1. The production of prostaglandin E(2) (PGE(2)) was quantified by ELISA method. Our results showed that 6% cyclic mechanical stretch significantly inhibited IL-1β-induced MMP-1 (gene) and COX-2 (gene and protein) expression at 15, 40, and 80 min. It also downregulated the IL-1β-induced production of PGE(2). Further investigation of nuclear factor kappa B (NF-κB) signal pathway-related effectors IκB-α and IκB-β revealed that 6% cyclic stretch inhibited their IL-1β-induced degradation in cytoplasm as well as reversed their gene transcription levels. Our data suggest that gentle level of cyclic mechanical stretch exerts a protective effect on RA-FLS as it downregulates the level of MMP-1 protease, COX-2, and proinflammatory PGE(2). The underlying mechanism appears to be, in part, executed through NF-κB and its upstream effectors.
authors.affiliation: Key Laboratory of Biorheology Science and Technology under the ministry of Education, College of Bioengineering, Chongqing University , Chongqing , PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: You
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Gurinder K
authors.initials: GK
authors.lastname: Singh
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Wanqian
authors.initials: W
authors.lastname: Liu
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhang
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Lv
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical; D013582:Synovial Fluid / Q000166:cytology
chemical_list: C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; C000606204:NFKBIA protein, human; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; D015232:Dinoprostone