Aberrant integrin activation induces p38 MAPK phosphorylation resulting in suppressed Fas-mediated apoptosis in T cells: Implications for rheumatoid arthritis

Yu ping Lin, Chung Chen Su, Jyun Yuan Huang, Huan Chin Lin, Yu Jung Cheng, Ming Fei Liu, Bei Chang Yang

研究成果: Article同行評審

15 引文 斯高帕斯(Scopus)

摘要

Delayed Fas-mediated apoptosis in T cells is associated with inflammatory diseases including rheumatoid arthritis (RA). CD3+ T cells in RA synovia expressed high amounts of phospho-p38 MAPK. Exposure to RA synovial fluid or soluble collagen, a degradation product of extracellular matrix abundant in RA synovium, induced the phosphorylation of p38 MAPK in Jurkat T cells accompanied by resistance against Fas-mediated apoptosis. Blocking β1 integrin by antibody diminished this effect. In addition, ectopic expression of auto-activated β1 integrin variant in T cells profoundly induced the phosphorylation of p38 MAPK. Suppression of p38 MAPK sensitized T cells to Fas-mediated apoptosis and increased caspase-8 and caspase-3 cleavage. A physical interaction of p38 MAPK and caspase-8 was demonstrated by using confocal microscopic imaging and co-immunoprecipitation assay. RA synovial fluid markedly increased the formation of phospho-p38 MAPK/caspase-8 complex in Jurkat T cells. In conclusion, abnormal activation of p38 MAPK to prevent Fas-mediated apoptosis may represent a common survival mechanism of RA synovial T cells contributing to the persistent inflammation of affected synovium. Crown

原文English
頁(從 - 到)3328-3335
頁數8
期刊Molecular Immunology
46
發行號16
DOIs
出版狀態Published - 2009 10月

All Science Journal Classification (ASJC) codes

  • 免疫學
  • 分子生物學

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