NDLI: CCL2 shapes macrophage polarization by GM-CSF and M-CSF: identification of CCL2/CCR2-dependent gene expression profile.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Sánchez-Torres, Carmen Barroso, Rubén Mellado, Mario López-Bravo, María Nieto, Concha Rodríguez-Fernández, José L. Puig-Kroger, Amaya Sierra-Filardi, Elena Joven, Jorge Corbí, Angel L. Sánchez-Mateos, Paloma Domínguez-Soto, Angeles Ardavín, Carlos
Description	Author Affiliation: Sierra-Filardi E ( Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid 28040, Spain)
Abstract	The CCL2 chemokine mediates monocyte egress from bone marrow and recruitment into inflamed tissues through interaction with the CCR2 chemokine receptor, and its expression is upregulated by proinflammatory cytokines. Analysis of the gene expression profile in GM-CSF- and M-CSF-polarized macrophages revealed that a high CCL2 expression characterizes macrophages generated under the influence of M-CSF, whereas CCR2 is expressed only by GM-CSF-polarized macrophages. Analysis of the factors responsible for this differential expression identified activin A as a critical factor controlling the expression of the CCL2/CCR2 pair in macrophages, as activin A increased CCR2 expression but inhibited the acquisition of CCL2 expression by M-CSF-polarized macrophages. CCL2 and CCR2 were found to determine the extent of macrophage polarization because CCL2 enhances the LPS-induced production of IL-10, whereas CCL2 blockade leads to enhanced expression of M1 polarization-associated genes and cytokines, and diminished expression of M2-associated markers in human macrophages. Along the same line, Ccr2-deficient bone marrow-derived murine macrophages displayed an M1-skewed polarization profile at the transcriptomic level and exhibited a significantly higher expression of proinflammatory cytokines (TNF- , IL-6) in response to LPS. Therefore, the CCL2-CCR2 axis regulates macrophage polarization by influencing the expression of functionally relevant and polarization-associated genes and downmodulating proinflammatory cytokine production.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	8
Volume Number	192
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-04-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Chemokine Ccl2 Genetics Granulocyte-macrophage Colony-stimulating Factor Pharmacology Macrophage Colony-stimulating Factor Macrophages Drug Effects Metabolism Activins Animals Chemokine Ccl8 Cluster Analysis Gene Expression Regulation Lipopolysaccharides Immunology Mice Mice, Knockout Monocytes Receptors, Ccr2 Transcriptome Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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