Investigation into the signal transduction pathway via which heat stress impairs intestinal epithelial barrier...

Intact protein absorption is thought to be a causative factor in several intestinal diseases, such as food allergy, celiac disease and inflammatory bowel disease. However, the mechanism remains unclear. The aim of this study was to characterize a novel signal transduction pathway via which heat stress compromises intestinal epithelial barrier function.

Heat stress was carried out by exposing confluent human intestinal epithelial cell line T84 cell monolayers to designated temperatures (37-43 degrees C) for 1 h. Transepithelial electric resistance (TER) and permeability to horseradish peroxidase (HRP, molecular weight = 44 000) were used as indicators to assess the intestinal epithelial barrier function. Phosphorylated myosin light chain (MLC), MLC kinase (MLCK) and protein kinase C (PKC) protein of the T84 cells were evaluated in order to identify the signal transduction pathway in the course of heat stress-induced intestinal epithelial barrier dysfunctions.

The results showed that exposure to heat stress significantly increased intact protein transport across the intestinal epithelial monolayer; the amount of phospho-PKC, phospho-MLCK and phospho-MLC proteins in T84 cells decreased significantly at 41 degrees C and 43 degrees C although they increased at 39 degrees C. The heat stress-induced T84 monolayer barrier dysfunction was inhibited by pretreatment with PKC inhibitor, MLCK inhibitor, or HSP70.

Heat stress can induce intestinal epithelial barrier dysfunction via the PKC and MLC signal transduction pathway.