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

作者：Lin Yu ping; Su Chung Chen; Huang Jyun Yuan; Lin Huan Chin; Cheng Yu Jung; Liu Ming Fei; Yang Bei Chang^*

来源：Molecular Immunology, 2009, 46(16): 3328-3335.

DOI：10.1016/j.molimm.2009.07.021

• Integrin
• p38 MAPK
• Rheumatoid arthritis
• Fas/Apo-1/CD95
• Apoptosis

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 beta 1 integrin by antibody diminished this effect. In addition, ectopic expression of auto-activated beta 1 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.

• 出版日期2009-10