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

World J Gastroenterol. 2013 Aug 14;19(30):4925-34. doi: 10.3748/wjg.v19.i30.4925.


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.

Keywords: Apoptosis; Intestine; Mucosa; Tumor necrosis factor-α; c-Jun N-terminal kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Apoptosis
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Disease Models, Animal
  • Enzyme Activation
  • Ileum / drug effects
  • Ileum / enzymology
  • Ileum / immunology*
  • Ileum / pathology
  • Infliximab
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / enzymology
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / pathology
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Jejunum / drug effects
  • Jejunum / enzymology
  • Jejunum / immunology*
  • Jejunum / pathology
  • Ligation
  • Male
  • Mesenteric Arteries / surgery
  • Mesenteric Vascular Occlusion / complications
  • Pentoxifylline / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / enzymology
  • Reperfusion Injury / etiology
  • Reperfusion Injury / genetics
  • Reperfusion Injury / immunology*
  • Reperfusion Injury / pathology
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*


  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • JNK Mitogen-Activated Protein Kinases
  • Casp3 protein, rat
  • Casp9 protein, rat
  • Caspase 3
  • Caspase 9
  • Pentoxifylline