Induction of macrophage Ia antigen expression by rIFN-γ and down-regulation by IFN-α/β and dexamethasone are mediated by changes in steady-state levels of Ia mRNA

In previous studies, the induction of Ia antigens on murine peritoneal exudate macrophages by recombinant IFN-γ (rIFN-γ) and the antagonism of rIFN-γ-induced Ia expression by the inhibitors IFN-α/β and glucocorticoids have been examined. In this report, these findings have been extended to an analysis of total or cytoplasmic mRNA from macrophage cultures treated with rIFN-γ in the absence or presence of these two inhibitors. Recombinant IFN-γ induced a 5.7- to 6.5-fold increase in steady-state levels of Ia (A(α)-specific) mRNA. Coordinate increases in steady-state mRNA for A(β), and E(α) were observed in response to rIFN-γ. Maximum induction occurred 24 hr post-treatment and required the continued presence of rIFN-γ. Induction of A(α)-specific mRNA was sensitive to the protein synthesis inhibitor cycloheximide. Simultaneous treatment of macrophage cultures with rIFN-γ and IFN-α/β or the glucocorticoid dexamethasone (DEX) resulted in a significant decrease in steady-state, A(α)-specific mRNA levels compared with treatment with rIFN-γ alone. This analysis suggests that both the induction of Ia expression by rIFN-γ, and the antagonism of rIFN-γ-induced Ia gene expression by IFN-α/β and DEX, are regulated by cognate changes in Ia mRNA.