Clinical Usefulness of Glucocorticoid Receptor beta Expression and NF-kappa B Activity in Patients with Ulcerative Colitis

Kim, Kyu Jong; Myung, Seung Jae; Hong, Seong Soo; Lee, Yun Jung; Lee, Sun Mi; Byeon, Jeong Sik; Yang, Suk Kyun; Hong, Weon Seon; Kim, Jin Ho; Min, Young Il

Abstract

BACKGROUND/AIMS: Glucocorticoid resistance poses a challenging clinical problem in inflammatory bowel disease because more than one fourth of patients with severe ulcerative colitis do not respond to anti-inflammatory steroids. Recently, it has been reported that glucocorticoid response is related to the expression of human glucocorticoid receptor beta (hGRbeta) and nuclear factor-kappa B (NF-kappaB) activity. The aims of this study were to clarify whether these factors may predict the responsiveness before treatment. METHODS: Total RNA was extracted from peripheral blood mononuclear cell (PBMC) and colonic mucosa in 17 patients of ulcerative colitis before steroid administration. RNA was reverse transcribed and the resulting complementary DNA was amplified using specific primers for hGR alpha and beta. Concomitantly, NF-kappaB activity in colonic mucosa was assessed by immunohistochemical stain. RESULTS: The expression of hGRbeta mRNA was detected in 10 patients (58.8%) in PBMC and 8 patients (47.1%) in colon, respectively. Operations were performed in 5 patients due to steroid unresponsiveness. Only 5 of 17 patients (29.4%) were consistent in the expression of hGRbeta between PBMC and colon. Seven of 15 patients (46.7%) showed an alteration in the expression of hGRbeta in PBMC after glucocorticoid treatment. NF-kappaB activity was found in both epithelial cell and lamina propria in 12, epithelial cell alone in 1, lamina propria alone in 1 and all negative in 3 patients, respectively. CONCLUSIONS: The expression of hGRbeta was discordant between PBMC and colon in the same patient and showed a change in the expession after the glucocorticoid treatment in nearly half. The expression of hGRbeta and colonic NF-kappaB activity patterns do not provide useful information about glucocorticoid response in patients with ulcerative colitis.