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 (Fc gamma R)-mediated binding and phagocytosis of immunoglobulin G-opsonized erythrocytes in mouse peritoneal exudate macrophages. Glucocorticoids potentiated this effect. We have extended these observations to an investigation of the effects of IFN-gamma and glucocorticoids on steady-state mRNA levels of the three Fc gamma R genes expressed on murine macrophages: Fc gamma RI, Fc gamma RII, and Fc gamma RIII alpha. Fc gamma RI mRNA was present at a barely detectable level in unstimulated cells but was induced 5- to 10-fold by IFN-gamma. Fc gamma RIII alpha mRNA was expressed constitutively and was induced significantly but very modestly (1.5-fold) by IFN-gamma. Fc gamma RII mRNA also exhibited high constitutive expression, but it was not altered by IFN-gamma treatment. Dexamethasone (DEX) significantly increased the expression of IFN-gamma-induced Fc gamma RI mRNA but had no effect on the expression of Fc gamma RII or Fc gamma RIII alpha transcripts in untreated or IFN-gamma-treated cells. The effect of DEX on Fc gamma RI 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 the Fc gamma RI mRNA, suggesting that the up-regulatory effect of DEX may occur, in part, at the level of transcription. In the same culture system, the steady-state level of IFN-gamma-induced Ia mRNA was concurrently inhibited by DEX. The up-regulation of the IFN-gamma-induced high-affinity Fc gamma RI mRNA, the failure to modulate the expression of the two low-affinity Fc gamma R mRNA species, and the down-regulation of IFN-gamma-induced Ia mRNA by DEX in the same cell population illustrate the diverse, gene-specific influence of glucocorticoids on the expression of IFN-gamma-inducible genes.
Sivo
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Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
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Vogel
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D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D005938:Glucocorticoids / Q000494:pharmacology*; D006207:Half-Life; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D010586:Phagocytes / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
D005938:Glucocorticoids; D012333:RNA, Messenger; D017452:Receptors, IgG; D003907:Dexamethasone; D007371:Interferon-gamma