Cycloheximide, an inhibitor of protein synthesis, prevents gamma-interferon-induced expression of class II mRNA in a macrophage cell line.

To characterize the mechanisms by which interferon gamma (IFN-gamma) upregulates major histocompatibility complex class II mRNA levels in mouse macrophages, we studied the effect of IFN-gamma on the transcription rate of class II genes and investigated the requirement for ongoing protein synthesis for the induction of class II mRNA expression. Nuclear run-off assays demonstrate that IFN-gamma induces class II mRNA at the transcriptional level. Treatment with cycloheximide, an inhibitor of protein synthesis, prevented the IFN-gamma-mediated accumulation of E alpha mRNA in the mouse macrophage cell line P388 D.1, indicating that induction of E alpha mRNA in P388 D.1 cells requires de novo synthesis of a protein intermediate. Our studies suggest that this putative protein factor is labile and required throughout the induction period.