Overexpression of GRβ in colonic mucosal cell line partly reflects altered gene expression in colonic mucosa of patients with inflammatory bowel disease

The glucocorticoid receptor (GR) plays a crucial role in inflammatory responses. GR has several isoforms, of which the most deeply studied are the GR alpha and GR beta. Recently it has been suggested that in addition to its negative dominant effect on GR alpha, the GR beta may have a GR alpha-independent transcriptional activity. The GR beta isoform was found to be frequently overexpressed in various autoimmune diseases, including inflammatory bowel disease (IBD). In this study, we wished to test whether the gene expression profile found in a GR beta overexpressing intestinal cell line (Caco-2GR beta) might mimic the gene expression alterations found in patients with IBD. Whole genome microarray analysis was performed in both normal and GR beta overexpressing Caco-2 cell lines with and without dexamethasone treatment. IBD-related genes were identified from a meta-analysis of 245 microarrays available in online microarray deposits performed on intestinal mucosa samples from patients with IBD and healthy individuals. The differentially expressed genes were further studied using in silico pathway analysis. Overexpression of GR beta altered a large proportion of genes that were not regulated by dexamethasone suggesting that GR beta may have a GR alpha-independent role in the regulation of gene expression. About 10% of genes differentially expressed in colonic mucosa samples from IBD patients compared to normal subjects were also detected in Caco-2 GR beta intestinal cell line. Common genes are involved in cell adhesion and cell proliferation. Overexpression of GR beta in intestinal cells may affect appropriate mucosal repair and intact barrier function. The proposed novel role of GR beta in intestinal epithelium warrants further studies. (C) 2015 Elsevier Ltd. All rights reserved.