PT  - JOURNAL ARTICLE
AU  - Yuko Okazaki
AU  - Tetsuji Sawada
AU  - Katsuya Nagatani
AU  - Yoshinori Komagata
AU  - Tetsufumi Inoue
AU  - Susumu Muto
AU  - Akiko Itai
AU  - Kazuhiko Yamamoto
TI  - Effect of nuclear factor-kappaB inhibition on rheumatoid fibroblast-like synoviocytes and collagen induced arthritis.
DP  - 2005 Aug 01
TA  - The Journal of Rheumatology
PG  - 1440--1447
VI  - 32
IP  - 8
4099  - http://www.jrheum.org/content/32/8/1440.short
4100  - http://www.jrheum.org/content/32/8/1440.full
SO  - J Rheumatol2005 Aug 01; 32
AB  - 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.