Alteration in intestine tight junction protein phosphorylation and apoptosis is associated with increase in IL-18 levels following alcohol intoxication and burn injury

作者：Li Xiaoling; Akhtar Suhail; Choudhry Mashkoor A^*

来源：Biochimica et Biophysica Acta-Molecular Basis of Disease, 2012, 1822(2): 196-203.

DOI：10.1016/j.bbadis.2011.09.019

• Thermal injury
• Inflammatory mediator
• Gut barrier
• Tissue damage
• Ethanol
• Cytokine

Intestinal mucosal barrier is the first line of defense against bacteria and their products originating from the intestinal lumen. We have shown a role for IL-18 in impaired gut barrier function following acute alcohol (EtOH) intoxication combined with burn injury. To further delineate the mechanism, this study examined whether IL-18 alters intestine tight junction proteins or induces mucosal apoptosis under these conditions. To accomplish this, rats were gavaged with EtOH (3.2 g/kg) prior to similar to 12.5% total body surface area burn or sham injury. One day after injury. EtOH combined with burn injury resulted in a significant decrease in total occludin protein and its phosphorylation in small intestine compared to either EtOH or burn injury alone. There was no change in claudin-1 protein content but its phosphorylation on tyrosine was decreased following EtOH and burn injury. This was accompanied with an increase in mucosal apoptosis (p%26lt;0.05). The treatment of rats with anti-IL-18 antibody at the time of burn injury prevented intestine apoptosis and normalized tight junction proteins following EtOH and burn injury. Altogether, these findings suggest that IL-18 modulates tight junction proteins and cause apoptosis leading to impaired intestinal mucosal integrity following EtOH intoxication combined with burn injury.

• 出版日期2012-2