title: Reactive oxygen species induce Cox-2 expression via TAK1 activation in synovial fibroblast cells.
abstract: Oxidative stress within the arthritis joint has been indicated to be involved in generating mediators for tissue degeneration and inflammation. COX-2 is a mediator in inflammatory action, pain and some catabolic reactions in inflamed tissues. Here, we demonstrated a direct relationship between oxidative stress and Cox-2 expression in the bovine synovial fibroblasts. Furthermore, we elucidated a novel mechanism, in which oxidative stress induced phosphorylation of MAPKs and NF-κB through TAK1 activation and resulted in increased Cox-2 and prostaglandin E2 expression. Finally, we demonstrated that ROS-induced Cox-2 expression was inhibited by supplementation of an antioxidant such as N-acetyl cysteamine and hyaluronic acid in vitro and in vivo. From these results, we conclude that oxidative stress is an important factor for generation of Cox-2 in synovial fibroblasts and thus its neutralization may be an effective strategy in palliative therapy for chronic joint diseases.
authors.affiliation: Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Onodera
authors.affiliation: Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Teramura
authors.affiliation: Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takehara
authors.affiliation: Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Shigi
authors.affiliation: Division of Cell Biology for Regenerative Medicine, Institute of Advanced Clinical Medicine, Kindai University Faculty of Medicine, Osaka, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Fukuda
keywords: COX, cyclooxygenase; Cox-2; HA, hyaluronic acid; NAC, N-acetyl cysteamine; OA model; OA, osteoarthritis; PGs, prostaglandins; RA, rheumatoid arthritis; ROS, reactive oxygen species; Reactive oxygen species; SFs, synovial fibroblast cells; Synovial tissues; TAK1