Association of GILZ with MUC2, TLR2, and TLR4 in Inflammatory Bowel Disease

Abstract

Ulcerative colitis (UC) and Crohn's Disease (CD) are chronic relapsing inflammatory diseases that are caused by genetic, environmental, and immune factors. Treatment strategies are currently based on symptomatic control by immunosuppression. The glucocorticoid-induced leucine zipper (GILZ), a mediator of several effects of glucocorticoids, was recently found to be secreted by goblet cells and play a role in inflammatory bowel disease (IBD). This study investigates which genes <i>GILZ</i> is associated with in its role in intestinal barrier functions. We examined datasets from the Gene Expression Omnibus (GEO) and ArrayExpress profiles of the gut of healthy subjects (HSs), as well as UC and CD patients. The human colonic epithelial HT29 cell line was used for in vitro validation experiments. <i>GILZ</i> was significantly correlated with <i>MUC2</i>, <i>TLR2</i>, and <i>TLR4</i>. In particular, an inverse correlation was found between the <i>GILZ</i> and <i>MUC2</i> in HS and patients with IBD, mostly in those with an active disease. Further, direct pairwise correlations for <i>GILZ</i>/<i>TLR2</i> and <i>GILZ</i>/<i>TLR4</i> were found in HSs and UC patients, but not in CD patients. Overall, our results reveal the crosstalk at the transcription level between the <i>GILZ</i>, <i>MUC2</i>, and <i>TLRs</i> in the mucosal barrier through common pathways, and they open up new perspectives in terms of mucosal healing in IBD patients.