Tsuboi M, Eguchi K, Kawakami A, Matsuoka N, Kawabe Y, Aoyagi T, Maeda K, Nagataki S
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Biochem Biophys Res Commun. 1996 Jan 5;218(1):280-5. doi: 10.1006/bbrc.1996.0049.
Recent reports revealed that Fas antigen is functionally expressed on human synovial cells and apoptosis can be induced in these cells by anti-Fas antibody. We examined the effect of interleukin 1 beta (IL-1 beta) on Fas antigen-mediated apoptosis on human synovial cells in vitro. Using flowcytometric analysis, IL-1 beta inhibited Fas antigen expression on synovial cells in a dose-dependent fashion. No significant difference of Fas antigen gene expression between IL-1 beta-treated and untreated synovial cells was observed by RT-PCR analysis, suggesting that the inhibitory effect of Fas antigen expression by IL-1 beta is at posttranscriptional level. Apoptosis of synovial cells was easily induced by treatment of these cells with anti-Fas antibody. In contrast, pretreatment of synovial cells with IL-1 beta protected these cells against Fas antigen-mediated apoptosis. The expression of bcl-2 on synovial cells, known to interfere with the apoptotic process mediated by the Fas antigen, was not influenced by IL-1 beta. Our results suggest that IL-1 beta inhibits Fas antigen-mediated apoptosis of synovial cells and may perpetuate the hyperplasia of the synovium in patients with rheumatoid arthritis.
最近的报告显示,Fas抗原在人滑膜细胞上有功能性表达,抗Fas抗体可诱导这些细胞发生凋亡。我们在体外研究了白细胞介素1β(IL-1β)对Fas抗原介导的人滑膜细胞凋亡的影响。通过流式细胞术分析,IL-1β以剂量依赖的方式抑制滑膜细胞上Fas抗原的表达。通过逆转录聚合酶链反应(RT-PCR)分析,未观察到IL-1β处理组和未处理组滑膜细胞之间Fas抗原基因表达有显著差异,这表明IL-1β对Fas抗原表达的抑制作用处于转录后水平。用抗Fas抗体处理滑膜细胞很容易诱导其凋亡。相反,用IL-1β预处理滑膜细胞可保护这些细胞免受Fas抗原介导的凋亡。已知可干扰Fas抗原介导的凋亡过程的bcl-2在滑膜细胞上的表达不受IL-1β影响。我们的结果表明,IL-1β抑制Fas抗原介导的滑膜细胞凋亡,可能使类风湿性关节炎患者滑膜的增生持续存在。