Rosiglitazone reduces a wide range of proinflammatory profiles in synovial fibroblast SW982 under spheroid culture.
Rosiglitazone (RSG) has been known to play a role in the modulation of inflammatory responses. Therefore, we sought to elucidate the underlying molecular mechanism by which RSG regulates the development of rheumatoid arthritis. Firstly, we examined the preventive effect of RSG on the inflammatory mediators induced by spheroid culture of synovial sarcoma SW982. Expression of proinflammatory cytokines under spheroid culture was more elevated than that under monolayer culture while RSG abolished inflammatory responses. The upregulation of inflammation-related genes by spheroid culture was closely associated with NFkappaB (NFkappaB) activation. Also, activation of p38 and c-Jun N-terminal kinase (JNK) by spheroid culture was abrogated with RSG treatment. Lastly, it was demonstrated that RSG reduced the development of arthritis in mice immunized with collagen, improving the histology of inflamed joint. In summary, RSG reduces inflammatory responses of synovial fibroblast via not only inhibition of NFkappaB but also modulation of both p38 and JNK.
Song
Jin Sook
JS
Drug Discovery Platform Technology Team, Bio-organic Science Division, Korea Research Institute of Chemical Technology, Sinseongno 19, Yuseong-gu, Daejeon, South Korea.
Kim
Chi Hyun
CH
Heo
Jun Young
JY
Cho
Young Sik
YS
D000818:Animals; D000843:Ankle Joint / Q000187:drug effects / Q000473:pathology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D000077154:Rosiglitazone; D018874:Spheroids, Cellular / Q000187:drug effects* / Q000276:immunology; D013583:Synovial Membrane / Q000166:cytology* / Q000187:drug effects*; D045162:Thiazolidinediones / Q000494:pharmacology*; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone