メソトレキサートによるRA滑膜線維芽細胞の細胞死誘導に関する研究

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  • Anti-rheumatic effect of Methotrexate through Apoptosis of Rheumatoid Synovial Fibroblasts

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In order to investigate the mechanism of antirheumatic action of methotrexate (MTX), antiproliferative effect of MTX on synovial fibroblasts obtained from rheumatoid arthritis (RA) patients were investigated. To examine the effect of MTX on DNA synthesis, total radioactivity of 3H-deoxyuridine (^3H-UdR) incorporated into the synovial fibroblasts was measured. Also quantification of DNA fragmentation of synovial fibroblasts in the cultured super-natant and cell associated Bcl-2 protein, Fas antigen which is suspected of modulating apoptosis, were performed with enzyme-linked immunosorbent assay. MTX suppressed synovial fibroblast proliferation in a dose dependent fashion. Significant inhibition (P<0.01) was attained at the concentration of more than 10<-8> M of MTX. Also, induction of DNA fragmentation which is characteristic of apoptosis were observed at over 10<-9> M MTX over 96 h-incubation significantly, which might be due to the suppression of Bcl-2 expression and decreasing IL-1β induced soluble Fas antigen release by MTX. These results, therefore, suggest that MTX may suppress the growth of rheumatoid pannus by inhibition of synovial fibroblast proliferation through the induction of apoptosis of synovial fibroblast with modulating Bcl-2 expression and soluble Fas antigen release in situ.

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