4.8 Article

Expression of glucocorticoid receptor β in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis

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GASTROENTEROLOGY
卷 118, 期 5, 页码 859-866

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W B SAUNDERS CO
DOI: 10.1016/S0016-5085(00)70172-7

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Background & Aims. Recently, the glucocorticoid receptor beta (hGR beta) was suggested to play a role as a dominant negative regulator for determining glucocorticoid response. The aim of this study was to clarify whether reverse-transcription polymerase chain reaction (RT-PCR) analysis of hGR beta messenger RNA (mRNA) can predict the response to glucocorticoids in patients with ulcerative colitis. Methods: Total RNA obtained from peripheral blood mononuclear cells (PBMCs) of 23 patients with ulcerative colitis and 20 healthy volunteers was reverse transcribed; the resulting complementary DNA was amplified using specific primers for hGR alpha and hGR beta. Protein expression of hGR in PBMCs was confirmed by immunoprecipitation-Western blot analysis. Results: The expression of hGR alpha mRNA (477 base pairs) was detected in all patients and all healthy volunteers, In contrast, a hGR beta mRNA (366 base pairs) was detected in 1 (9.1%) of 11 glucocorticoid-sensitive patients, 10 (83.3%) of 12 glucocorticoid-resistant patients, and 2 (10%) of 20 healthy volunteers. The positive rate of hGR beta mRNA in the resistant group was significantly higher than that in the sensitive group (P = 0.0019). The hGR beta band could be detected by immunoprecipitation-Western blotting in hGR beta mRNA-positive patients. Conclusions: The results show that the expression of hGR beta mRNA in PBMCs examined by RT-PCR may serve as a novel predictor of glucocorticoid response in ulcerative colitis.

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