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• W2030435705 abstract "Objective Recent studies have shown the importance of proteasome function in the regulation of apoptosis. This study examined whether inhibition of proteasome function mediates apoptosis of synovial cells, and whether cytokines modulate this process. Methods Type B synovial cells (fibroblast-like synovial cells) were cultured with tumor necrosis factor α (TNFα) or transforming growth factor β1 (TGFβ1), and further incubated in the presence of variable concentrations of Z-Leu-Leu-Leu-aldehyde (LLL-CHO), a proteasome inhibitor. During this process, apoptosis of synovial cells was determined by Hoechst 33258 dye staining and 51Cr release assay. The involvement of caspase cascade was examined using enzyme activity assay and blocking experiments by peptide inhibitors. The expression of pro-caspases, Bcl-2–related proteins, and X chromosome–linked inhibitor of apoptosis (XIAP) in synovial cells was examined by Western blot analysis. Results Apoptosis of cultured synovial cells was induced in a dose-dependent manner by LLL-CHO. Activation of caspase cascade through caspase-8 to caspase-3 was essential during this process. Pretreatment of synovial cells with TNFα significantly augmented both the activation of caspases and the proportion of apoptosis in synovial cells induced by LLL-CHO, whereas TGFβ1 pretreatment markedly suppressed these phenomena. The ratio of the expression of Bcl-2 to Bax or Bcl-xL to Bax, and XIAP expression in synovial cells may not be directly associated with the susceptibility of synovial cells to apoptosis by LLL-CHO. Conclusion Apoptosis of synovial cells was induced by inhibition of proteasome function through the activation of caspase cascade, and this process was clearly modulated by cytokines. These data provide new insight into the regulatory mechanisms controlling synovial cells in rheumatoid synovitis by proteasome inhibitors, and might be useful for the design of new therapeutic strategies in rheumatoid arthritis." @default.
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• W2030435705 date "1999-11-01" @default.
• W2030435705 modified "2023-09-26" @default.
• W2030435705 title "Regulation of synovial cell apoptosis by proteasome inhibitor" @default.
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• W2030435705 doi "https://doi.org/10.1002/1529-0131(199911)42:11<2440::aid-anr23>3.0.co;2-0" @default.
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