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Induction of CD36 and Thrombospondin-1 in Macrophages by Hypoxia-Inducible Factor 1 and Its Relevance in the Inflammatory Process

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Induction of CD36 and Thrombospondin-1 in Macrophages by Hypoxia-Inducible Factor 1 and Its Relevance in the Inflammatory Process

dc.contributor.author	Ortiz Masiá, María Dolores
dc.contributor.author	Díez, Irene
dc.contributor.author	Calatayud Romero, Sara
dc.contributor.author	Hernández, Carlos
dc.contributor.author	Cosín Roger, Jesús
dc.contributor.author	Esplugues Mota, Juan Vicente
dc.contributor.author	Barrachina Sancho, María Dolores
dc.date.accessioned	2015-11-17T13:19:55Z
dc.date.available	2015-11-17T13:19:55Z
dc.date.issued	2012
dc.identifier.uri	http://hdl.handle.net/10550/48235
dc.description.abstract	Inflammation is part of a complex biological response of vascular tissue to pathogens or damaged cells. First inflammatory cells attempt to remove the injurious stimuli and this is followed by a healing process mediated principally by phagocytosis of senescent cells. Hypoxia and p38-MAPK are associated with inflammation, and hypoxia inducible factor 1 (HIF-1) has been detected in inflamed tissues. We aimed to analyse the role of p38-MAPK and HIF-1 in the transcriptional regulation of CD36, a class B scavenger receptor, and its ligand thrombospondin (TSP-1) in macrophages and to evaluate the involvement of this pathway in phagocytosis of apoptotic neutrophils. We have also assessed HIF-1α, p38-MAPK and CD36 immunostaining in the mucosa of patients with inflammatory bowel disease. Results show that hypoxia increases neutrophil phagocytosis by macrophages and induces the expression of CD36 and TSP-1. Addition of a p38-MAPK inhibitor significantly reduced the increase in CD36 and TSP-1 expression provoked by hypoxia and decreased HIF-1α stabilization in macrophages. Transient transfection of macrophages with a miHIF-1α-targeting vector blocked the increase in mRNA expression of CD36 and TSP-1 during hypoxia and reduced phagocytosis, thus highlighting a role for the transcriptional activity of HIF-1. CD36 and TSP-1 were necessary for the phagocytosis of neutrophils induced by hypoxic macrophages, since functional blockade of these proteins undermined this process. Immunohistochemical studies revealed CD36, HIF-1α and p38-MAPK expression in the mucosa of patients with inflammatory bowel disease. A positive and significant correlation between HIF-1α and CD36 expression and CD36 and p38-MAPK expression was observed in cells of the lamina propria of the damaged mucosa. Our results demonstrate a HIF-1-dependent up-regulation of CD36 and TSP-1 that mediates the increased phagocytosis of neutrophils by macrophages during hypoxia. Moreover, they suggest that CD36 expression in the damaged mucosa of patients with inflammatory bowel disease depends on p38-MAPK and HIF-1 activity.
dc.language.iso	eng
dc.relation.ispartof	Plos One, 2012, vol. 7, num. 10
dc.source	Ortiz Masià, M. Dolores Díez, Irene Calatayud, Sara Hernandez, Carlos Cosin Roger, Jesús Esplugues, Juan V. Barrachina, Maria D. 2012 Induction of CD36 and Thrombospondin-1 in Macrophages by Hypoxia-Inducible Factor 1 and Its Relevance in the Inflammatory Process Plos One 7 10
dc.subject	Farmacologia
dc.subject	Venes Malalties
dc.title	Induction of CD36 and Thrombospondin-1 in Macrophages by Hypoxia-Inducible Factor 1 and Its Relevance in the Inflammatory Process
dc.type	journal article	es_ES
dc.date.updated	2015-11-17T13:19:55Z
dc.identifier.idgrec	066564
dc.rights.accessRights	open access	es_ES