MODULATION OF THE TRANSCRIPTIONAL RATE OF FC-GAMMA RECEPTOR MESSENGER-RNA IN HUMAN MONONUCLEAR PHAGOCYTES

Human monocytes and macrophages bear three classes of cell surface receptors for the Fc portion of IgG (FcγRI, FcγRII, and FCγRIII). These receptors mediate phagocytosis and other effector functions and are important in the pathophysiology of hematologic disease, inflammation, and host defense. We have previously shown that interferon-γ (IFN-γ) and dexamethasone modulate total FcγRII mRNA levels as well as FcγRI and FcγRII protein expression on monocytes and the monocyte-like cell line U937. In this study, we investigated the modulation of FcγRI mRNA. Additionally, we utilized mRNA stability and nuclear run-on assays to study the mechanism of the modulation of Fcγ receptor transcripts in the monocyte/macrophage cell line U937. In U937 cells, IFN-γ increased FcγRI mRNA levels 7.5-fold. Treatment with dexamethasone reduced FcγRI mRNA levels to 0.6-fold of baseline and inhibited by 20-60% the increase in mRNA observed after treatment of the U937 cells with IFN-γ. On monocytes, treatment with IFN-γ increased monocyte FcγRI mRNA 6.7-fold. Cotreatment of the IFN-γ-stimulated monocytes with dexamethasone resulted in a 160% further increase in FcγRI expression. FCγRI and FCγRII mRNA half-lives were then determined in U937 cells by incubation with dexamethasone and/or IFN-γ for 16 hr and then arresting mRNA transcription with actinomycin-D (10 μg/ml). The mRNA half-lives in untreated U937 cells were 3.3 ± 0.3 hr (FcγRI) and 3.1 ± 0.3 hr (FcγRII). For either FcγRI and FcγRII, the effect of dexamethasone and/or IFN-γ on mRNA half-life was not significant (P > 0.5). We also performed nuclear run-on experiments with U937 cells which indicated that IFN-γ increased the transcription of FcγRI 4.2-fold and FcγRII 1.7-fold. Our data suggest that these changes in FcγRI and FcγRII protein are likely due, at least in part, to increases in mRNA levels secondary to alteration in gene transcription. © 1992.