[Clinical usefulness of glucocorticoid receptor beta expression and NF-kappaB activity in patients with ulcerative colitis].
OBJECTIVE
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 hGR beta 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 hGR beta between PBMC and colon. Seven of 15 patients (46.7%) showed an alteration in the expression of hGR beta 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 hGR beta was discordant between PBMC and colon in the same patient and showed a change in the expression after the glucocorticoid treatment in nearly half. The expression of hGR beta and colonic NF-kappaB activity patterns do not provide useful information about glucocorticoid response in patients with ulcerative colitis.
Kim
Kyu-Jong
KJ
Division of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Myung
Seung-Jae
SJ
Hong
Seong Soo
SS
Lee
Yun Jung
YJ
Lee
Sun Mi
SM
Byeon
Jeong-Sik
JS
Yang
Suk-Kyun
SK
Hong
Weon Seon
WS
Kim
Jin-Ho
JH
Min
Young Il
YI
D000328:Adult; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003106:Colon / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*
D016328:NF-kappa B; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C121943:glucocorticoid receptor beta