Interferon-γ increases the expression of the gene encoding the β subunit of the granulocyte-macrophage colony-stimulating factor receptor

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) activates a broad range of myeloid cells through binding to high-affinity receptors (GM-CSF-R) consisting of at least two distinct subunits, GM-CSF-Rα and GM-CSF-Rβ. The genes of these GM-CSF-R subunits have been identified recently, but little is known about the regulation of their expression. In this study, we investigated the expression of the GM-CSF-R subunit genes in normal human monocytes. Out of a panel of various cytokines and factors tested, only interferon-γ (IFN-γ) affected the expression of one of the GM-CSF-R subunit genes by increasing the GM-CSF-Rβ mRNA expression threefold to sixfold with no effect on GM-CSF-Rα. Maximal effects occurred 2 to 4 hours after stimulation with 500 to 5,000 U/mL IFN-γ. Nuclear run-on assays and mRNA half-life studies showed that IFN-γ modestly enhanced the transcription of the GM-CSF-Rβ gene and stabilized the GM-CSF-Rβ mRNA, with the latter mechanism predominant. Pretreatment of the monocytes with cycloheximide did not abrogate the increase of GM-CSF-Rβ mRNA expression induced by IFN-γ, indicating that de novo protein synthesis was not required for this activity. When monocytes were exposed to IFN-γ for 6 to 24 hours, the number of GM-CSF-R per cell was increased 79% as compared with controls, whereas the receptor affinity remained unchanged. These data indicate that the GM-CSF-R expression in monocytes may be upregulated by IFN-γ via an increased expression of the β subunit gene, involving both transcriptional and posttranscriptional mechanisms. © 1992 by The American Society of Hematology.