Effects of rapamycin on apoptosis of rheumatoid synovial cells.
In the present study, we investigated the effects of an immunosuppressant, rapamycin, on bcl-2 expression and the susceptibility of human rheumatoid synovial fibroblasts to Fas-mediated apoptosis. Rapamycin treatment down-regulated bcl-2 expression on rheumatoid synovial cells in a dose-dependent manner. In contrast, Fas antigen expression was not influenced by rapamycin treatment. Rapamycin treatment also enhanced the susceptibility of rheumatoid synovial cells to anti-Fas monoclonal antibody-mediated apoptosis. Our results suggest that rapamycin augments the sensitivity of rheumatoid synovial fibroblasts to apoptosis by down-regulating bcl-2 expression. This pharmacological alteration of sensitivity to apoptosis in the rheumatoid synovium may represent a new therapeutic approach for rheumatoid arthritis.
Migita
K
K
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Eguchi
K
K
Ichinose
Y
Y
Kawabe
Y
Y
Tsukada
T
T
Aoyagi
T
T
Nagataki
S
S
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011090:Polyenes / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000187:drug effects; D020123:Sirolimus; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*; D019014:fas Receptor / Q000276:immunology
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011090:Polyenes; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D020123:Sirolimus