Published online Aug 14, 2013. doi: 10.3748/wjg.v19.i30.4925
Revised: May 31, 2013
Accepted: June 19, 2013
Published online: August 14, 2013
AIM: To investigate whether tumor necrosis factor-α (TNF-α) 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-α inhibitor, pentoxifylline, or the TNF-α 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-α 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-α 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-α at both the mRNA and protein levels, whereas infliximab pretreatment did not affect the expression of TNF-α 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-α-mediated JNK activation response to intestinal I/R injury.
Core tip: Ischemia-reperfusion (I/R) injury is a critical physiopathological phenomenon wherein further damage may occur when the blood supply of ischemic organs is recovered, and the mechanism of I/R remains unclear. This paper demonstrates that tumor necrosis factor-α (TNF-α) played a pivotal role in intestinal I/R injury, and pretreatment with the TNF-α inhibitor pentoxifylline or the TNF-α antibody infliximab remarkably attenuated I/R-induced injury by inhibiting TNF-α-mediated apoptosis and c-Jun N-terminal kinase (JNK) activation. The results of the study indicate there is a TNF-α-mediated JNK activation response to intestinal I/R injury.