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Platelet activating factor promotes mucosal apoptosis via FasL mediating caspase‐9 active pathway in rat small intestine after ischemia‐reperfusion
Author(s) -
Wu Bin,
Iwakiri Ryuichi,
Ootani Akifumi,
Fujise Takehiro,
Tsunada Seiji,
Fujimoto Kazuma
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0499fje
Subject(s) - fas ligand , platelet activating factor , apoptosis , cytochrome c , chemistry , proinflammatory cytokine , caspase 3 , microbiology and biotechnology , endocrinology , biology , pharmacology , medicine , inflammation , immunology , programmed cell death , biochemistry
Platelet activating factor (PAF) is a proinflammatory lipid mediator for inflammatory response. It is unclear whether PAF is involved in the very complex process of ischemia‐reperfusion (I/R) induced mucosal apoptosis in small intestine. Intestinal I/R was induced in rats intestine by 60 min occlusion of the superior mesenteric artery, followed by a 60 min reperfusion. I/R induced mucosal apoptosis and PAF activity but inhibited PAF‐acetylhydrolase activity. Increases in interleukin‐6 (IL‐6) and decreases in IL‐10 were observed. Western blot analysis showed that I/R induced expressions of platelet endothelial cell adhesion molecule‐1 (PECAM‐1) and Fas and Fas ligand (FasL) proteins, cleaved Bid, and enhanced the release of cytochrome c from mitochondria to activate caspase‐9. Pretreatment of PAF antagonist BN‐52021 attenuated these changes, except the increase in Fas. The results showed that I/R‐inhibited mucosal PAF‐acetylhydrolase activity resulted in an increase of activated PAF. The activated PAF increased the mucosal IL‐6 and PECAM‐1, enhanced the expression of FasL but not Fas, and led to the cleavage of Bid and the release of cytochrome c from mitochondria to activate caspase‐9. This finding suggests that PAF promotes mucosal apoptosis after I/R in the rat small intestine partly through FasL mediating caspase‐9 active pathway.