Quantitative analysis for human glucocorticoid receptor alpha/beta mRNA in IBD.
We have previously reported that in peripheral blood mononuclear cells (PBMC), the augmented expression of the beta isoform of the human glucocorticoid receptor (hGRbeta), as a putative dominant negative regulator of glucocorticoid action, is associated with glucocorticoid (GC) unresponsiveness of UC patients. In this study, we quantified the levels and serial changes of hGR transcripts in PBMC of IBD patients by a real-time fluorescence monitoring of PCR. As results, relative hGRbeta mRNA expression was significantly higher in the active stage of UC than in inactive periods of UC or CD patients. Longitudinal analysis revealed that hGRbeta mRNA expression in UC was increased after the relapse of inflammation, suggesting that the overproduction of cytokines during inflammation may be responsible. In in vitro culture experiments of human lymphoid cell (CEM) and human PBMC, IL-7, and IL-18 increased hGRbeta mRNA expression in these cells but GC itself did not. Through these analyses, it is indicated that the inflammatory cytokines altered the splicing condition of the primary transcript of hGR gene in IBD patients.
Third Department of Internal Medicine, Asahikawa Medical College, 2-1 Midorigaoka-higashi, Hokkaido 078-8510, Asahikawa, Japan.
Fumika
F
Orii
Toshifumi
T
Ashida
Masafumi
M
Nomura
Atsuo
A
Maemoto
Takanori
T
Fujiki
Tokiyoshi
T
Ayabe
Shinjiro
S
Imai
Yusuke
Y
Saitoh
Yutaka
Y
Kohgo
D000328:Adult; D002460:Cell Line; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D020382:Interleukin-18 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D019169:Jurkat Cells; D008137:Longitudinal Studies; D008297:Male; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000235:genetics*; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
D005938:Glucocorticoids; D020382:Interleukin-18; D015851:Interleukin-7; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; D003907:Dexamethasone