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 (CR) e xpression was studied in HOS-8603 cells, a human osteogenic sarcoma ce ll line. Treatment of HOS-8603 cells with IFN resulted in down-regulat ion of CR number, with no change in the binding affinity for glucocort icoids. The maximum decrease in receptor binding was evident at 10 IU/ ml IFN concentration. Time-course studies revealed that the effect rea ched a maximum at 36 h treatments. To clarify the molecular basis for the down-regulation of CR by IFN, change in GR mRNA levels was further investigated by RNA blot hybridization analysis. It was found that th ere also existed a time-dependent decrease in CR mRNA levels in HOS-86 03 cells after treatment with IFN. In the presence of IFN, the inhibit ory effect of glucorticoids on HOS-8603 cell proliferation was blunted . Moreover, the induction of alkaline phosphatase (AKP) activity by gl ucocorticoids was attenuated in response to IFN treatment. These data suggest that IFN may influence GR activity which at least partially oc curs at mRNA levels, and that the decrease in receptor activity in HOS -8603 tells parallels with the decrease in glucocorticoid-mediated fun ctional responses.