PMID: 9558092Apr 29, 1998Paper

Selective inhibition of expression of the chemokine receptor CCR2 in human monocytes by IFN-gamma

The Journal of Immunology : Official Journal of the American Association of Immunologists
G Penton-RolA Mantovani

Abstract

IFN-gamma is a potent activator of mononuclear phagocyte function and promotes the development of Th1 responses. Moreover, it induces and modulates chemokine production in a variety of cell types, including mononuclear phagocytes. In the present study, we examined the effect of IFN-gamma on the expression of CC chemokine receptors in human monocytes. IFN-gamma selectively and rapidly inhibited expression of the monocyte chemotactic protein (MCP) receptor CCR2 with an ED50 of approximately 50 U/ml. The effect was rapid (detectable after 1 h) and reversible. Other chemokine receptors (CCR1, CCR3, CCR4, and CCR5) were not substantially affected, and CXCR4 was reduced. IFN-gamma acted in concert with LPS, TNF-alpha, and IL-1beta in inhibiting CCR2 expression. IFN-gamma-treated monocytes showed a shorter half-life of CCR2 mRNA compared with untreated cells, whereas the rate of nuclear transcription was unaffected. The inhibition of CCR2 mRNA expression by IFN-gamma was associated with a lower number of surface receptors and lower chemotactic responsiveness. Thus, IFN-gamma, an inducer of MCP-1 and MCP-3 in mononuclear phagocytes, selectively inhibits expression of the MCP receptor CCR2 in monocytes. These results are consistent with...Continue Reading

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