title: Alteration in intestine tight junction protein phosphorylation and apoptosis is associated with increase in IL-18 levels following alcohol intoxication and burn injury.
abstract: 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 (3.2g/kg) prior 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<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.
authors: Department of Surgery, Loyola University Chicago Stritch School of Medicine, 2160 South First Ave, Maywood, IL 60153, USA.
authors: Xiaoling
authors: X
authors: Li
authors: Suhail
authors: S
authors: Akhtar
authors: Mashkoor A
authors: MA
authors: Choudhry
mesh_terms: D000435:Alcoholic Intoxication / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002056:Burns / Q000150:complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D062445:Claudin-1; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007421:Intestine, Small / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D019108:Tight Junctions / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000906:Antibodies; D062445:Claudin-1; C568114:Cldn1 protein, rat; D020382:Interleukin-18; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D014443:Tyrosine; D053148:Caspase 3