Multiple pathways of interferon-induced gene expression in murine macrophages

Steady-state levels of mRNAs that encode specific Fc gamma R and Ia antigen genes have been measured in macrophages treated with interferons (IFNs) to examine the induction of these markers at the molecular level. Our previous studies suggested requirement for protein kinase C (PKC) in the IFN induction of these macrophage surface markers, although a difference in PKC dependence was found between IFN-alpha/beta- and IFN-gamma-induced Fc gamma R expression. The protein kinase antagonist H7, used previously to distinguish between the surface induction of Fc gamma R by IFN-alpha/beta and IFN-gamma, also distinguishes between the IFN-alpha and IFN-gamma in the induction of Fc gamma RI mRNA and Fc gamma RI surface expression. Protein kinase inhibitors blocked the IFN-gamma induction of Ia mRNA in a manner similar to that reported previously for cell surface Ia expression. It is concluded that Fc gamma RI is induced by both IFN-alpha and IFN-gamma through distinct biochemical pathways, whereas IFN-gamma utilizes distinct pathways to induce the two macrophage activation markers, Ia antigen and Fc gamma RI.