Gamma interferon down-regulates glucocorticoid receptor expression and attenuates hormone action in a human osteosarcoma cell line.

The effect of gamma interferon (IFN) on glucocorticoid receptor (GR) expression was studied in HOS-8603 cells, a human osteogenic sarcoma cell line. Treatment of HOS-8603 cells with IFN resulted in down-regulation of GR number, with no change in the binding affinity for glucocorticoids. The maximum decrease in receptor binding was evident at 10 IU/ml IFN concentration. Time-course studies revealed that the effect reached a maximum at 36 h treatments. To clarify the molecular basis for the down-regulation of GR by IFN, change in GR mRNA levels was further investigated by RNA blot hybridization analysis. It was found that there also existed a time-dependent decrease in GR mRNA levels in HOS-8603 cells after treatment with IFN. In the presence of IFN, the inhibitory effect of glucorticoids on HOS-8603 cell proliferation was blunted. Moreover, the induction of alkaline phosphatase (AKP) activity by glucocorticoids was attenuated in response to IFN treatment. These data suggest that IFN may influence GR activity which at least partially occurs at mRNA levels, and that the decrease in receptor activity in HOS-8603 cells parallels with the decrease in glucocorticoid-mediated functional responses.