HEAT-SHOCK MIMICS GLUCOCORTICOID EFFECTS ON IFN-GAMMA-INDUCED FC-GAMMA-RI AND IA MESSENGER-RNA EXPRESSION IN MOUSE PERITONEAL-MACROPHAGES

Glucocorticoids activate or repress the expression of different genes. In murine macrophages, glucocorticoids exert opposing effects on the IFN-gamma-induced expression of Fc gamma RI and Ia mRNA and cell surfa ce expression; they enhance IFN-gamma-induced Fc gamma RI mRNA and pro tein expression, yet inhibit IFN-gamma-induced Ia mRNA and protein exp ression. Recently, in transfected cell lines, heat shock (HS) has been shown to promote nuclear accumulation of the glucocorticoid receptor (GR), resulting in potentiation of certain GR-mediated responses. In t his study, we compared the effects of HS and dexamethasone (DEX) treat ment on the IFN-gamma induction of Fc gamma RI and Ia mRNA in murine p rimary peritoneal macrophages. Our results show that HS exerted the sa me opposing effects on these IFN-gamma-responsive genes as DEX at 37 d egrees C. The glucocorticoid antagonist RU 486 blocked bath DEX and HS -induced enhancement of IFN-gamma induction of Fc gamma RI, suggesting a common GR-mediated mechanism. While RU 486 also reversed DEX-induce d repression of Ia mRNA expression, supporting a GR-mediated action, i t did not affect HS-mediated repression, raising the possibility of a ligand-independent HS response pathway.