INVOLVEMENT OF SIMULTANEOUS MULTIPLE TRANSCRIPTION FACTOR EXPRESSION,INCLUDING CAMP-RESPONSIVE ELEMENT-BINDING PROTEIN AND OCT-1, FOR SYNOVIAL CELL OUTGROWTH IN PATIENTS WITH RHEUMATOID-ARTHRITIS

Objective-To elucidate possible roles of several transcription factors in the pathogenesis of rheumatoid arthritis (RA), the transcription f actor expression in RA synovial tissue and their contribution to RA sy novial cell functions were studied. Methods-Single cell suspension of dissociated synovial tissue was cultured to induce in vitro tissue out growth of RA synovial cells. Transcription factors were immunohistoche mically identified in RA synovial tissue obtained by joint surgery and in the in vitro tissue outgrowth, and confirmed by western blotting a nd gel shift assays. Results-Immunohistochemical examination of RA syn ovial tissue revealed simultaneous expression of various transcription factors (NF-KB, c-Jun (a component of AP-1), cAMP responsive element binding protein (CREB), and OCT-1). The same set of transcription fact ors was expressed in the in vitro tissue outgrowth of RA patients. The early passage RA synovial cells were treated with interleukin 1 beta (IL1 beta) and confirmed translocation of transcription factors into t he nucleus by western blotting, and their DNA binding activity by gel shift assays. Conclusion-This study emphasises the importance of the s imultaneous expression of several transcription factors for the hypera ctivity of RA synovial cells that leads to tissue outgrowth.