Aberrant integrin activation induces p38 MAPK phosphorylation resulting in suppressed Fas-mediated apoptosis in T cells: Implications for rheumatoid arthritis |
| |
Authors: | Yu-ping Lin Chung-Chen Su Jyun-Yuan Huang Huan-Chin Lin Yu-Jung Cheng Ming-Fei Liu Bei-Chang Yang |
| |
Affiliation: | aInstitute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan, ROC;bDepartment of Microbiology & Immunology, National Cheng Kung University, Tainan, Taiwan, ROC;cInner Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC;dCenter for Gene Regulation and Signal Transduction Research, National Cheng Kung University, Tainan, Taiwan, ROC |
| |
Abstract: | 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. |
| |
Keywords: | Integrin p38 MAPK Rheumatoid arthritis Fas/Apo-1/CD95 Apoptosis |
本文献已被 ScienceDirect 等数据库收录! |
|