DIFFERENTIAL-EFFECTS OF INTERFERON-GAMMA AND GLUCOCORTICOIDS ON FC-GAMMA-R GENE-EXPRESSION IN MURINE MACROPHAGES

Interferon-gamma (IFN-gamma) was shown previously to increase Fc-gamma receptor (FcgammaR)-mediated binding and phagocytosis of immunoglobul in G-opsonized erythrocytes in mouse peritoneal exudate macrophages Gl ucocorticoids potentiated this effect. We have extended these observat ions to an investigation of the effects of IFN-gamma and glucocorticoi ds on steady-state mRNA levels of the three FcgammaR genes expressed o n murine macrophages: FcgammaRI, FcgammaRII, and FcgammaRIIIalpha. Fcg ammaRI mRNA was present at a barely detectable level in unstimulated c ells but was induced 5- to 10-fold by IFN-gamma. FcgammaRIIIalpha mRNA was expressed constitutively and was induced significantly but very m odestly (1.5-fold) by IFN-gamma. FCgammaRII mRNA also exhibited high c onstitutive expression, but it was not altered by IFN-gamma treatment. Dexamethasone (DEX) significantly increased the expression of IFN-gam ma-induced FcgammaRI mRNA but had no effect on the expression of Fcgam maRII or FcgammaRIIIalpha transcripts in untreated or IFN-gamma-treate d cells. The effect of DEX on FcgammaRI mRNA was seen after about 10 h of simultaneous treatment with IFN-gamma, was dose-dependent, and was glucocorticoid specific. DEX did not modulate the rate of decay of th e FcgammaRI mRNA, suggesting that the up-regulatory effect of DEX may occur, in part, at the level of transcription. In the same culture sys tem, the steady-state level of IFN-gamma-induced Ia mRNA was concurren tly inhibited by DEX. The up-regulation of the IFN-gamma-induced high- affinity FcgammaRI mRNA, the failure to modulate the expression of the two low-affinity FcgammaR mRNA species, and the downregulation of IFN -gamma-induced Ia mRNA by DEX in the same cell population illustrate t he diverse, gene-specific influence of glucocorticoids on the expressi on of IFN-gamma-inducible genes.