Vascular endothelial growth factor expression is associated with B cell activating factor production stimulated with tumor necrosis factor-α in MH7A human synovial cells (P6280)

Abstract

Listen

Translate article

Abstract Rheumatoid arthritis (RA), one of autoimmune diseases, is characterized by histological hallmarks such as hyperplasia of the synovial lining cells, mononuclear cell infiltration, angiogenesis, and osteoclastic bone destruction. Angiogenesis is mediated through expression of vascular endothelial growth factor (VEGF) in RA synovium. VEGF expression is enhanced by TNF-α, the main pro-inflammatory cytokine in RA. B cell activating factor (BAFF) which plays a role in maturation and maintenance of B cells is also associated with autoimmune RA. Here, we investigated whether BAFF could regulate VEGF expression in MH7A synovial cells that is established by transfection with the SV40 T antigen (Miyazawa et al., 1998). When MH7A cells were treated with TNF-α, data showed that TNF-α increased the expression of BAFF and VEGF as judged by western blotting, RT-PCR and luciferase promoter assay. Inhibition of BAFF expression with BAFF-siRNA decreased VEGF expression. In addition, BAFF and VEGF expression was mediated by nuclear translocation of c-Fos activated by the treatment with TNF-α as judged by the transfection of MH7A cells with c-fos-siRNA. In conclusion, our results suggest for the first time that angiogenesis in RA could be controlled by BAFF-mediated VEGF expression.