Inhibition of fas antigen‐mediated apoptosis of rheumatoid synovial cells in vitro by transforming growth factor β1

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Abstract
Objective. To investigate the mitogenic and anti‐apoptotic effects of transforming growth factor β1 (TGFβ) on rheumatoid synovial cells in vitro. Methods. Synovial cells were cultured with or without TGFβ1. After incubation, the proliferative response of synovial cells and the expression of Fas antigen and bcl‐2 on synovial cells were examined. Finally, Fas antigen‐mediated apoptosis of synovial cells was investigated by the addition of anti‐Fas antibody. Results. TGFβ1 enhanced the proliferation of synovial cells in a dose‐dependent manner. In addition, Fas antigen expression on synovial cells was inhibited by the addition of TGFβ1 with up‐regulation of bcl‐2 expression. The addition of anti‐Fas antibody induced synovial cell apoptosis. However, stimulation of synovial cells with TGFβ1 became markedly resistant to Fas antigen‐mediated apoptosis. The results were not affected by the addition of a neutralizing antibody to platelet‐derived growth factor type AA (PDGF‐AA), which suggests that the effect of TGFβ1 on synovial cells was promoted via PDGF‐AA‐independent mechanisms. Conclusion. Our results suggest that TGFβ1 promotes synovial cell proliferation through its mitogenic effect on synovial cells and interference with the apoptotic process mediated by the Fas antigen, resulting in the perpetuation of the synovial hyperplasia in patients with rheumatoid arthritis.