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IFN-gamma up-regulates platelet-activating factor receptor gene expression in human monocytes.
J Immunol. 1994 May 15; 152(10):5092-9.JI

Abstract

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.

Authors+Show Affiliations

Department of Pediatrics, Faculty of Medicine, University of Sherbrooke, Québec, Canada.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8176225

Citation

Ouellet, S, et al. "IFN-gamma Up-regulates Platelet-activating Factor Receptor Gene Expression in Human Monocytes." Journal of Immunology (Baltimore, Md. : 1950), vol. 152, no. 10, 1994, pp. 5092-9.
Ouellet S, Müller E, Rola-Pleszczynski M. IFN-gamma up-regulates platelet-activating factor receptor gene expression in human monocytes. J Immunol. 1994;152(10):5092-9.
Ouellet, S., Müller, E., & Rola-Pleszczynski, M. (1994). IFN-gamma up-regulates platelet-activating factor receptor gene expression in human monocytes. Journal of Immunology (Baltimore, Md. : 1950), 152(10), 5092-9.
Ouellet S, Müller E, Rola-Pleszczynski M. IFN-gamma Up-regulates Platelet-activating Factor Receptor Gene Expression in Human Monocytes. J Immunol. 1994 May 15;152(10):5092-9. PubMed PMID: 8176225.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IFN-gamma up-regulates platelet-activating factor receptor gene expression in human monocytes. AU - Ouellet,S, AU - Müller,E, AU - Rola-Pleszczynski,M, PY - 1994/5/15/pubmed PY - 1994/5/15/medline PY - 1994/5/15/entrez SP - 5092 EP - 9 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 152 IS - 10 N2 - 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. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/8176225/IFN_gamma_up_regulates_platelet_activating_factor_receptor_gene_expression_in_human_monocytes_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=8176225 DB - PRIME DP - Unbound Medicine ER -