Abstract
IFN-γ 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-γ on the expression of CC chemokine receptors in human monocytes. IFN-γ selectively and rapidly inhibited expression of the monocyte chemotactic protein (MCP) receptor CCR2 with an ED50 of ~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-γ acted in concert with LPS, TNF-α, and IL-1β in inhibiting CCR2 expression. IFN-γ- 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-γ was associated with a lower number of surface receptors and lower chemotactic responsiveness. Thus, IFN- γ, 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 an emerging paradigm of divergent regulation by several agents of chemokine production and receptor expression in monocytes. The inhibition of MCP-1R expression may serve as a means of retaining mononuclear phagocytes at sites of inflammation and as a feedback mechanism in the regulation of recruitment from the blood.
| Original language | English |
|---|---|
| Pages (from-to) | 3869-3873 |
| Number of pages | 5 |
| Journal | Journal of Immunology |
| Volume | 160 |
| Issue number | 8 |
| Publication status | Published - Apr 15 1998 |
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ASJC Scopus subject areas
- Immunology
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Selective inhibition of expression of the chemokine receptor CCR2 in human monocytes by IFN-γ. / Penton-Rol, Giselle; Polentarutti, Nadia; Luini, Walter; Borsatti, Alessandro; Mancinelli, Roberta; Sica, Antonio; Sozzani, Silvano; Mantovani, Alberto.
In: Journal of Immunology, Vol. 160, No. 8, 15.04.1998, p. 3869-3873.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Selective inhibition of expression of the chemokine receptor CCR2 in human monocytes by IFN-γ
AU - Penton-Rol, Giselle
AU - Polentarutti, Nadia
AU - Luini, Walter
AU - Borsatti, Alessandro
AU - Mancinelli, Roberta
AU - Sica, Antonio
AU - Sozzani, Silvano
AU - Mantovani, Alberto
PY - 1998/4/15
Y1 - 1998/4/15
N2 - IFN-γ 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-γ on the expression of CC chemokine receptors in human monocytes. IFN-γ selectively and rapidly inhibited expression of the monocyte chemotactic protein (MCP) receptor CCR2 with an ED50 of ~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-γ acted in concert with LPS, TNF-α, and IL-1β in inhibiting CCR2 expression. IFN-γ- 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-γ was associated with a lower number of surface receptors and lower chemotactic responsiveness. Thus, IFN- γ, 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 an emerging paradigm of divergent regulation by several agents of chemokine production and receptor expression in monocytes. The inhibition of MCP-1R expression may serve as a means of retaining mononuclear phagocytes at sites of inflammation and as a feedback mechanism in the regulation of recruitment from the blood.
AB - IFN-γ 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-γ on the expression of CC chemokine receptors in human monocytes. IFN-γ selectively and rapidly inhibited expression of the monocyte chemotactic protein (MCP) receptor CCR2 with an ED50 of ~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-γ acted in concert with LPS, TNF-α, and IL-1β in inhibiting CCR2 expression. IFN-γ- 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-γ was associated with a lower number of surface receptors and lower chemotactic responsiveness. Thus, IFN- γ, 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 an emerging paradigm of divergent regulation by several agents of chemokine production and receptor expression in monocytes. The inhibition of MCP-1R expression may serve as a means of retaining mononuclear phagocytes at sites of inflammation and as a feedback mechanism in the regulation of recruitment from the blood.
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UR - http://www.scopus.com/inward/citedby.url?scp=0032522651&partnerID=8YFLogxK
M3 - Article
C2 - 9558092
AN - SCOPUS:0032522651
VL - 160
SP - 3869
EP - 3873
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 8
ER -