Regulation of connexin expression in intestinal epithelial cells during experimental inflammatory bowel disease

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of an unknown cause. Studies have identified connexins (Cxs) of gap junctions as important targets of proinflammatory mediators, many of which are altered in IBD. In this study we evaluated, in an animal model, the effect of experimental IBD on the expression of Cxs in the descending colon.Inflammation was intra‐rectally induced in 70 male Sprague‐Dawley rats using three different treatments: Iodoacetamide, Iodoacetamide + bacteria (Enteropathogenic E.coli) and bacteria. Animals were clinically monitored and tissues were collected for histological studies. Transcriptional expression levels of cytokines and Cxs were assayed by RT‐PCR, and protein levels and localization of Cxs by western blotting and immunohistochemistry.A significant upregulation in the gene expression of IL‐1ß was observed in the descending colon mucosa with a slight increase in the levels of TNFα mRNA and a decrease in the protein expression of Cx32 and Cx43. However, upregulation of Cx43 protein was detected at some time points, presumably due to the infiltration of inflammatory cells that express Cx43. Immunoreactivity against Cx32 and Cx43 confirmed the expression of these proteins in intestinal epithelial cells of the colonic crypts.The decrease in the expression of Cx proteins may limit the spread of inflammation, but may contribute adversely to IBD by disrupting the epithelial barrier.