Glucocorticoid receptor expression in inflammatory bowel disease: evidence for a mucosal down-regulation in steroid-unresponsive ulcerative colitis.

Abstract

Glucocorticoids (GC) play a major role in the attenuation of inflammation. Glucocorticoid receptor (GR) expression is an important determinant of steroid sensitivity. To investigate whether GR mRNA expression is altered in inflammatory bowel disease, and whether GR mRNA expression correlates with disease activity and may predict response to GC therapy. Mucosal biopsies were taken from 33 patients with ulcerative colitis, 21 with Crohn's disease and 11 controls. Peripheral blood mononuclear cells were isolated from 24 ulcerative colitis and 18 Crohn's disease patients and 11 controls. GR mRNA was measured by quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and correlated to endoscopic findings, clinical activity and outcome of GC therapy. In a subset of subjects GR localisation was shown by immunohistochemistry. In patients with inflammatory bowel disease GR expression was not different from controls. However, GR was decreased in biopsies from ulcerative colitis patients with impaired GC response. The inhibitory subtype GRbeta was expressed 100-1000 times lower than GRalpha. GR immunoreactivity was identified in immune and epithelial cells except for colonic crypts. In inflammatory bowel disease systemic and mucosal GR mRNA expression is not altered. However, in ulcerative colitis patients, low mucosal GR expression may predict the outcome of GC therapy. The low expression of GRbeta challenges its role in steroid refractoriness in inflammatory bowel disease.