Authors: | Li, X; Akhtar, S; Choudhry, M. A. |
Article 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 (p0.05). 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. Copyright Copyright 2011 Elsevier B.V. All rights reserved. |
Journal Title: | Biochimica et biophysica acta |
Volume: | 1822 |
Issue: | 2 |
ISSN: | 0006-3002; 0006-3002 |
Publisher: | Elsevier Inc |
Journal Place: | Netherlands |
Date Published: | 2012 |
Start Page: | 196 |
End Page: | 203 |
Language: | English |
DOI/URL: | |
Notes: | ID: 12452; Record Owner: From MEDLINE, a database of the U.S. National Library of Medicine.; Status: MEDLINE; Publishing Model: Journal available in: Print-Electronic Citation processed from: Print; NLM Journal Code: a0w, 0217513; Other ID: Source: NLM. NIHMS345305 [Available on 02/01/13] Source: NLM. PMC3261659 [Available on 02/01/13]; CAS Registry/EC Number/Name of Substance: 0 (Antibodies). 0 (Interleukin-18). 0 (Membrane Proteins). 0 (claudin 1). 0 (occludin). 55520-40-6 (Tyrosine). EC 3-4-22 (Caspase 3).; Grant Number: R01 AA015731-01A2 (United States NIAAA NIH HHS), R01AA015731 (United States NIAAA NIH HHS), R21 AA015979-01A1 (United States NIAAA NIH HHS), R21AA015979 (United States NIAAA NIH HHS); Electronic Date of Publication: 20111007; Entry Date: 20120710 |