OBJECTIVE: The purpose of this study was to determine whether glucocorticoids can block the induction of HLA-DR antigen expression by interferon gamma in human fibroblasts in culture. DESIGN AND PATIENTS: Confluent cultures of fibroblasts derived from the orbit or the skin of patients with Graves' ophthalmopathy or from normal subjects were treated with interferon gamma (100 U/ml) without or with graded concentrations of steroids. MEASUREMENTS: Cultures were analysed for HLA-DR expression using quantitative immunoblotting and indirect immunofluorescence. RESULTS: Glucocorticoids could block HLA-DR induction in a dose-dependent manner. At 10(-6) mol/l, the steroids dexamethasone and RU 28362 inhibited expression by 70% (P < 0.004) and 56% (P < 0.002) respectively. RU 38486, a glucocorticoid antagonist, could reverse the effect of both glucocorticoids, an action that was also dose dependent. At 10(-5) mol/l, RU 38486 blocked virtually the entire glucocorticoid effect. CONCLUSIONS: These results suggest that glucocorticoids can regulate HLA-DR induction by interferon gamma at physiological concentrations, an action which is stereospecific and mediated through the glucocorticoid receptor.
OBJECTIVE: The purpose of this study was to determine whether glucocorticoids can block the induction of HLA-DR antigen expression by interferon gamma in human fibroblasts in culture. DESIGN AND PATIENTS: Confluent cultures of fibroblasts derived from the orbit or the skin of patients with Graves' ophthalmopathy or from normal subjects were treated with interferon gamma (100 U/ml) without or with graded concentrations of steroids. MEASUREMENTS: Cultures were analysed for HLA-DR expression using quantitative immunoblotting and indirect immunofluorescence. RESULTS: Glucocorticoids could block HLA-DR induction in a dose-dependent manner. At 10(-6) mol/l, the steroidsdexamethasone and RU 28362 inhibited expression by 70% (P < 0.004) and 56% (P < 0.002) respectively. RU 38486, a glucocorticoid antagonist, could reverse the effect of both glucocorticoids, an action that was also dose dependent. At 10(-5) mol/l, RU 38486 blocked virtually the entire glucocorticoid effect. CONCLUSIONS: These results suggest that glucocorticoids can regulate HLA-DR induction by interferon gamma at physiological concentrations, an action which is stereospecific and mediated through the glucocorticoid receptor.
Authors: Iwona J Bujalska; Omar M Durrani; Joseph Abbott; Claire U Onyimba; Pamela Khosla; Areeb H Moosavi; Tristan T Q Reuser; Paul M Stewart; Jeremy W Tomlinson; Elizabeth A Walker; Saaeha Rauz Journal: J Endocrinol Date: 2007-02 Impact factor: 4.286