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Effects of rapamycin on apoptosis of rheumatoid synovial cells
K Migita1, K Eguchi, Y Ichinose
1First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Abstract:
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.
Insights
Rapamycin, an immunosuppressant, reduces bcl-2 expression in rheumatoid synovial cells. This enhances their susceptibility to apoptosis, offering a potential new therapy for rheumatoid arthritis.
Area of Science:
- Immunology
- Cell Biology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) involves chronic inflammation of the synovium.
- Synovial fibroblasts play a key role in RA pathogenesis.
- Targeting apoptosis in RA synovial cells is a potential therapeutic strategy.
Purpose of the Study:
- To investigate the effect of rapamycin on bcl-2 expression in human rheumatoid synovial fibroblasts.
- To determine if rapamycin influences the susceptibility of these cells to Fas-mediated apoptosis.
- To explore rapamycin's potential as a therapeutic agent for rheumatoid arthritis.
Main Methods:
- Human rheumatoid synovial fibroblasts were treated with varying doses of rapamycin.
- bcl-2 and Fas antigen expression levels were analyzed.
- Apoptosis susceptibility was assessed using anti-Fas monoclonal antibody treatment.
Main Results:
- Rapamycin treatment dose-dependently down-regulated bcl-2 expression in rheumatoid synovial cells.
- Fas antigen expression remained unaffected by rapamycin.
- Rapamycin enhanced the sensitivity of rheumatoid synovial cells to anti-Fas antibody-induced apoptosis.
Conclusions:
- Rapamycin increases the sensitivity of rheumatoid synovial fibroblasts to apoptosis by reducing bcl-2 expression.
- This modulation of apoptosis offers a potential novel therapeutic approach for rheumatoid arthritis.
- Targeting bcl-2 expression with rapamycin may be beneficial in managing RA.