NDLI: The prolyl hydroxylase PHD3 identifies proinflammatory macrophages and its expression is regulated by activin A.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Corbí, Angel L. Sánchez-Torres, Carmen Sánchez-Mateos, Paloma Calderon-Gómez, Elisabeth Nieto, Concha Matsuyama, Takami Escribese, María M. Vega, Miguel A. Samaniego, Rafael Salas, Azucena Sierra-Filardi, Elena
Description	Country affiliation: Spain Author Affiliation: Escribese MM ( Laboratorio de Células Mieloides, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid 28040, Spain. mescribese@cib.csic.es)
Abstract	Modulation of macrophage polarization underlies the onset and resolution of inflammatory processes, with polarization-specific molecules being actively sought as potential diagnostic and therapeutic tools. Based on their cytokine profile upon exposure to pathogenic stimuli, human monocyte-derived macrophages generated in the presence of GM-CSF or M-CSF are considered as proinflammatory (M1) or anti-inflammatory (M2) macrophages, respectively. We report in this study that the prolyl hydroxylase PHD3-encoding EGLN3 gene is specifically expressed by in vitro-generated proinflammatory M1(GM-CSF) human macrophages at the mRNA and protein level. Immunohistochemical analysis revealed the expression of PHD3 in CD163(+) lung macrophages under basal homeostatic conditions, whereas PHD3(+) macrophages were abundantly found in tissues undergoing inflammatory responses (e.g., Crohn's disease and ulcerative colitis) and in tumors. In the case of melanoma, PHD3 expression marked a subset of tumor-associated macrophages that exhibit a weak (e.g., CD163) or absent (e.g., FOLR2) expression of typical M2-polarization markers. EGLN3 gene expression in proinflammatory M1(GM-CSF) macrophages was found to be activin A dependent and could be prevented in the presence of an anti-activin A-blocking Ab or inhibitors of activin receptor-like kinase receptors. Moreover, EGLN3 gene expression was upregulated in response to hypoxia only in M2(M-CSF) macrophages, and the hypoxia-mediated upregulation of EGLN3 expression was significantly impaired by activin A neutralization. These results indicate that EGLN3 gene expression in macrophages is dependent on activin A both under basal and hypoxic conditions and that the expression of the EGLN3-encoded PHD3 prolyl hydroxylase identifies proinflammatory macrophages in vivo and in vitro.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Activins Metabolism Dioxygenases Gene Expression Regulation Immunology Inflammation Macrophages Enzymology Genetics Blotting, Western Enzyme-linked Immunosorbent Assay Hypoxia-inducible Factor-proline Dioxygenases Immunohistochemistry Microscopy, Confocal Real-time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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