Significance of glucocorticoid receptor expression in colonic mucosal cells of patients with ulcerative colitis.
OBJECTIVE
Glucocorticoid (GC) resistant ulcerative colitis (UC) remains a serious disease and is difficult to manage. Although the molecular basis of GC insensitivity is still unknown, GC receptors (GRalpha and GRbeta) may play an important role in it. This study was aimed to investigate the relationship between the expression of GRalpha and GRbeta in colonic mucosal cells of patients with UC, the efficacy of GC therapy and the intensity of inflammation.


METHODS
Twenty-five cases of UC were classified into: GC sensitive (n = 16) and GC resistant (n = 9) cases. Patients consisted of mild (n = 6), moderate (n = 8) and severe (n = 11) cases. GRalpha and GRbeta expression in colonic mucosal specimens were investigated by immunohistochemistry, and compared between GC resistant and sensitive groups, and also among various degrees of inflammation.


RESULTS
All cases were positive for GRalpha and GRbeta expression. Both positive association between GRalpha expression and the response of UC to GC and strong negative association between GRbeta expression and the response of UC to GC were identified. There was no significant association between GRalpha/GRbeta expression and the degree of inflammation of UC.


CONCLUSIONS
These findings suggest that both GRalpha and GRbeta may play an important role in the action of GC, and that GRbeta functions as a dominant negative inhibitor of GRalpha. Expression of GRalpha and GRbeta in colonic mucosal cells of patients with UC may serve as predictors of glucocorticoid response, but can not function as markers of inflammatory intensity.
Zhang
Hu
H
Department of Gastroenterology, Sichuan University West China Hospital, Chengdu 610041, Sichuan Province, China. tigerwcums@163.net
Ouyang
Qin
Q
Wen
Zhong-Hui
ZH
Fiocchi
Claudio
C
Liu
Wei-Ping
WP
Chen
Dai-Yun
DY
Li
Feng-Yuan
FY
D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D015415:Biomarkers; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta