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

doi:10.1136/ard.57.8.487

Annals of the Rheumatic Diseases 1998;57:487-494; doi:10.1136/ard.57.8.487

Ann Rheum Dis 1998;57:487-494 ( August )

Extended reports

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 Sueshige Wakisaka,^a Noboru Suzuki,^a Mitsuhiro Takeno,^a Yuko Takeba,^a Hiroko Nagafuchi,^a Nobuhiko Saito,^b Hideo Hashimoto,^c Tetsuya Tomita,^c Takahiro Ochi,^c Tsuyoshi Sakane^a

^a Departments of Immunology and Medicine, ^b and Department of Internal Medicine, ^c St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan Department of Orthopaedic Surgery, Osaka University School of Medicine, Osaka, Japan

Correspondence to: Dr T Sakane, Departments of Immunology and Medicine, St Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa 216, Japan.

Accepted for publication 21 May 1998

OBJECTIVE $---$ To elucidate possible roles of several transcription factors in the pathogenesis of rheumatoid arthritis (RA), the transcriptionfactor expression in RA synovial tissue and their contributionto RA synovial cell functions werestudied.
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 inRA synovial tissue obtained by joint surgery and in the in vitrotissue outgrowth, and confirmed by western blotting and gel shiftassays.
RESULTS $---$ Immunohistochemical examination of RA synovial tissue revealed simultaneous expression of various transcription factors (NF- $kappa$ B,c-Jun (a component of AP-1), cAMP responsive element binding protein(CREB), and OCT-1). The same set of transcription factors wasexpressed in the in vitro tissue outgrowth of RA patients. Theearly passage RA synovial cells were treated with interleukin1 $beta$ (IL1 $beta$ ) and confirmed translocation of transcription factorsinto the nucleus by western blotting, and their DNA binding activityby gel shiftassays.
CONCLUSION $---$ This study emphasises the importance of the simultaneous expression of several transcription factors for the hyperactivityof RA synovial cells that leads to tissueoutgrowth.

Keywords: synovial cells; cytokine; transcription factor; tissue outgrowth

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