TY - JOUR T1 - Effect of nuclear factor-kappaB inhibition on rheumatoid fibroblast-like synoviocytes and collagen induced arthritis. JF - The Journal of Rheumatology JO - J Rheumatol SP - 1440 LP - 1447 VL - 32 IS - 8 AU - Yuko Okazaki AU - Tetsuji Sawada AU - Katsuya Nagatani AU - Yoshinori Komagata AU - Tetsufumi Inoue AU - Susumu Muto AU - Akiko Itai AU - Kazuhiko Yamamoto Y1 - 2005/08/01 UR - http://www.jrheum.org/content/32/8/1440.abstract N2 - OBJECTIVE: The nuclear factor-kB (NF-kB) signaling pathway has been implicated as a molecular target for the treatment of various inflammatory diseases, such as rheumatoid arthritis (RA). In particular, IkB kinase (IKK) is considered an important molecular target because the majority of inflammatory signaling pathways mediated by NF-kB involve IKK activation. We investigated the effect of NF-kB inhibition on rheumatoid fibroblast-like synoviocytes (FLS) and collagen induced arthritis. METHODS: We evaluated the effect of IMD-0560, an inhibitor of IKK, on rheumatoid FLS in vitro and on collagen type II induced arthritis in mice. RESULTS: IMD-0560 suppressed the nuclear translocation of NF-kB and phosphorylation of IkBa induced by tumor necrosis factor-a in FLS. In addition, this compound suppressed the production of inflammatory cytokines, including interleukin 6 (IL-6), IL-8, and monocyte chemoattractant protein-1. IMD-0560 also inhibited the proliferation of FLS without showing cellular toxicity. Finally, this compound was effective against collagen induced arthritis in mice. CONCLUSION: Based on these results, IMD-0560 could be a new therapeutic agent for RA. ER -