Tumor necrosis factor-α mediates JNK activation response to intestinal ischemia-reperfusion injury

AIM: To investigate whether tumor necrosis factor-alpha (TNF-alpha) mediates ischemia-reperfusion (I/R)-induced intestinal mucosal injury through c-Jun N-terminal kinase (JNK) activation. METHODS: In this study, intestinal I/R was induced by 60-min occlusion of the superior mesenteric artery in rats followed by 60-min reperfusion, and the rats were pretreated with a TNF-alpha inhibitor, pentoxifylline, or the TNF-alpha antibody infliximab. After surgery, part of the intestine was collected for histological analysis. The mucosal layer was harvested for RNA and protein extraction, which were used for further real-time polymerase chain reaction, enzyme-linked immunosorbent assay and Western blotting analyses. The TNF-alpha expression, intestinal mucosal injury, cell apoptosis, activation of apoptotic protein and JNK signaling pathway were analyzed. RESULTS: I/R significantly enhanced expression of mucosal TNF-alpha at both the mRNA and protein levels, induced severe mucosal injury and cell apoptosis, activated caspase-9/caspase-3, and activated the JNK signaling pathway. Pretreatment with pentoxifylline markedly downregulated TNF-alpha at both the mRNA and protein levels, whereas infliximab pretreatment did not affect the expression of TNF-alpha induced by I/R. However, pretreatment with pentoxifylline or infliximab dramatically suppressed I/R-induced mucosal injury and cell apoptosis and significantly inhibited the activation of caspase-9/3 and JNK signaling. CONCLUSION: The results indicate there was a TNF-alpha-mediated JNK activation response to intestinal I/R injury. (c) 2013 Baishideng. All rights reserved.