IFN-gamma up-regulates platelet-activating factor receptor gene expression in human monocytes.
Human monocytes constitutively express the platelet-activating factor receptor (hPAF-R). In this report, we have investigated the modulation of hPAF-R by IFN-gamma. Treatment of monocytes with IFN-gamma caused a time- and concentration-dependent accumulation of hPAF-R mRNA. In contrast, IFN-alpha was inactive. The effect of IFN-gamma was rapid, evident by 1 h of stimulation and reaching a maximum after 2 h. The high level of hPAF-R mRNA was maintained for at least 24 h. Flow cytometry analysis revealed that monocytes treated with IFN-gamma had a two- to sixfold increase in PAF receptor expression at the cell surface, when compared with untreated cells. The increase in hPAF-R expression was associated with an augmented response of IFN-gamma-treated cells to PAF in terms of cytosolic calcium ([Ca2+]i) variations. The IFN-gamma-dependent accumulation of hPAF-R mRNA was not due to the stabilization of hPAF-R mRNA, as shown by unchanged hPAF-R mRNA t1/2. Pretreatment of monocytes with actinomycin D, however, completely abrogated the effect of IFN-gamma, suggesting a transcriptional regulation. Moreover, the up-regulation of hPAF-R mRNA by IFN-gamma was independent of de novo protein synthesis since cycloheximide, an inhibitor of protein synthesis, did not affect this up-regulation. These studies are the first report showing that IFN-gamma regulates hPAF-R gene expression in human monocytes, by a mechanism suggesting transcriptional regulation. This may represent a prototypic example of regulation by lymphocyte-derived cytokines of lipid mediator receptors in myeloid cells, thus adding a novel element in the interrelationship between immune and inflammatory responses.
Ouellet
S
S
Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Québec, Canada.
Müller
E
E
Rola-Pleszczynski
M
M
D001483:Base Sequence; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000032:analysis / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation
D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D007371:Interferon-gamma