Inhibition of Fas antigen-mediated apoptosis of rheumatoid synovial cells in vitro by transforming growth factor beta 1.
OBJECTIVE
To investigate the mitogenic and anti-apoptotic effects of transforming growth factor beta 1 (TGF beta 1) on rheumatoid synovial cells in vitro.


METHODS
Synovial cells were cultured with or without TGF beta 1. 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
TGF beta 1 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 TGF beta 1 with up-regulation of bcl-2 expression. The addition of anti-Fas antibody induced synovial cell apoptosis. However, stimulation of synovial cells with TGF beta 1 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 TGF beta 1 on synovial cells was promoted via PDGF-AA-independent mechanisms.


CONCLUSIONS
Our results suggest that TGF beta 1 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.
Kawakami
A
A
Nagasaki University School of Medicine, Japan.
Eguchi
K
K
Matsuoka
N
N
Tsuboi
M
M
Kawabe
Y
Y
Aoyagi
T
T
Nagataki
S
S
D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D019204:GTP-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008858:Microscopy, Phase-Contrast; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000032:analysis; D013583:Synovial Membrane / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D019014:fas Receptor / Q000235:genetics*
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D019014:fas Receptor; D019204:GTP-Binding Proteins