Wakisaka S, Suzuki N, Takeno M, Takeba Y, Nagafuchi H, Saito N, Hashimoto H, Tomita T, Ochi T, Sakane T
Department of Immunology and Medicine, St Marianna University School of Medicine, Kanagawa, Japan.
Ann Rheum Dis. 1998 Aug;57(8):487-94. doi: 10.1136/ard.57.8.487.
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 RA synovial cell functions were studied.
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.
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 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 the nucleus by western blotting, and their DNA binding activity by gel shift assays.
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.
为阐明几种转录因子在类风湿关节炎(RA)发病机制中的可能作用,对RA滑膜组织中的转录因子表达及其对RA滑膜细胞功能的作用进行了研究。
将解离的滑膜组织单细胞悬液进行培养,以诱导RA滑膜细胞的体外组织生长。通过关节手术获取的RA滑膜组织及体外组织生长物中,采用免疫组织化学方法鉴定转录因子,并通过蛋白质印迹法和凝胶迁移试验进行确认。
RA滑膜组织的免疫组织化学检查显示多种转录因子(核因子κB、c-Jun(激活蛋白-1的一个组分)、环磷酸腺苷反应元件结合蛋白(CREB)和八聚体转录因子-1)同时表达。在RA患者的体外组织生长物中也表达了相同的一组转录因子。用白细胞介素1β(IL1β)处理早期传代的RA滑膜细胞,通过蛋白质印迹法确认转录因子向细胞核的转位,并通过凝胶迁移试验检测其DNA结合活性。
本研究强调了几种转录因子同时表达对于导致组织生长的RA滑膜细胞过度活跃的重要性。