MULTIPLE PATHWAYS OF INTERFERON-INDUCED GENE-EXPRESSION IN MURINE MACROPHAGES

Steady-state levels of mRNAs that encode specific FcgammaR and la anti gen 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 IF N-gamma-induced FcgammaR expression. The protein kinase antagonist H7, used previously to distinguish between the surface induction of Fcgam maR by IFN-alpha/beta and IFN-gamma, also distinguishes between the IF N-alpha and IFN-gamma in the induction of FCgammaRI mRNA and FcgammaRI surface expression' Protein kinase inhibitors blocked the IFN-gamma i nduction of la mRNA in a manner similar to that reported previously fo r cell surface la expression. It is concluded that FCgammaRI is induce d by both IFN-alpha and IFN-gamma through distinct biochemical pathway s, whereas IFN-gamma utilizes distinct pathways to induce the two macr ophage activation markers, la antigen and FcgammaRI.