Tumor necrosis factor-α mediates JNK activation response to intestinal ischemia-reperfusion injury |
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基金项目: | Supported by Grants-in-Aid from the Major Projects Incubator Program of the National Key Basic Research Program of China,No. 2012CB526700;National Natural Science Foundation of China,No. 30971357;Natural Science Foundation of Guangdong Province,No. S2011020002348;Science and Technology Planning Project of Guangdong Province,No. 2009B060300001;Major Projects Incubator Program of SunYat-Sen University,No.10ykjc25 |
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摘 要: | 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 TNFα-mediated JNK activation response to intestinal I/R injury.
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关 键 词: | Tumor necrosis factor-α Intestine Mucosa Apoptosis c-Jun N-terminal kinase |
收稿时间: | March 13, 2013 |
Tumor necrosis factor-α mediates JNK activation response to intestinal ischemia-reperfusion injury |
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Authors: | Qi Yang Feng-Ping Zheng Ya-Shi Zhan Jin Tao Si-Wei Tan Hui-Ling Liu Bin Wu |
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Institution: | Qi Yang, Feng-Ping Zheng, Ya-Shi Zhan, Jin Tao, Si-Wei Tan, Hui-Ling Liu, Bin Wu, Department of Gastroenterology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China |
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Abstract: | 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. |
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Keywords: | Tumor necrosis factor-α Intestine Mucosa Apoptosis c-Jun N-terminal kinase |
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