Induction of macrophage Ia antigen expression by rIFN-gamma and down-regulation by IFN-alpha/beta and dexamethasone are regulated transcriptionally.

In previous studies, the induction of Ia Ag on murine macrophages by rIFN-gamma and the antagonism of this induction by IFN-alpha/beta and glucocorticoids were examined. These findings showed that both the induction of Ia Ag by rIFN-gamma, as well as the antagonism of rIFN-gamma-induced Ia Ag expression by IFN-alpha/beta and dexamethasone, are regulated by cognate changes in Ia mRNA. In the present report, this observation was first extended to show that the decreased steady-state level of Ia-specific mRNA seen in the cytoplasm of macrophages treated with rIFN-gamma in the presence of IFN-alpha/beta or dexamethasone were also seen in nuclear RNA preparations. To test the hypothesis that alterations in the rate of Ia gene transcription were responsible for these changes in steady-state levels, nuclear "run on" transcription experiments were performed. The results indicate that both the induction of Ia gene expression by rIFN-gamma and its inhibition by IFN-alpha/beta or dexamethasone are regulated by changes in Ia gene transcription.