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

Abstract

Objective - To elucidate possible roles of several transcription factors in the pathogenesis of rheumatoid arthritis (RA), the transcription factor expression in RA synovial tissue and their contribution to IRA synovial cell functions were studied. Methods - Single cell suspension of dissociated synovial tissue was cultured to induce in vitro tissue outgrowth of RA synovial cells. Transcription factors were immunohistochemically identified in RA synovial tissue obtained by joint surgery and in the in vitro tissue outgrowth, and confirmed by western blotting and gel shift assays. Results - Immunohistochemical examination of RA synovial tissue revealed simultaneous expression of various transcription factors (NF-κB, c-Jun (a component of AP-1), cAMP responsive element binding protein (GREB), and OCT-1). The same set of transcription factors was expressed in the in vitro tissue outgrowth of RA patients. The early passage RA synovial cells were treated with interleukin 1β (IL1β) and confirmed translocation of transcription factors into the nucleus by western blotting, and their DNA binding activity by gel shift assays. Conclusion - This study emphasises the importance of the simultaneous expression of several transcription factors for the hyperactivity of RA synovial cells that leads to tissue outgrowth.