title: Oxysterol mixture and, in particular, 27-hydroxycholesterol drive M2 polarization of human macrophages.
abstract: Macrophages play a crucial role in atherosclerosis progression. Classically activated M1 macrophages have been found in rupture-prone atherosclerotic plaques whereas alternatively activated macrophages, M2, localize in stable plaque. Macrophage accumulation of cholesterol and of its oxidized derivatives (oxysterols) leads to the formation of foam cells, a hallmark of atherosclerotic lesions. In this study, the effects of oxysterols in determining the functional polarization of human macrophages were investigated. Monocytes, purified from peripheral blood mononuclear cells of healthy donors, were differentiated into macrophages (M0) and treated with an oxysterol mixture, cholesterol, or ethanol, every 4 H for a total of 4, 8, and 12 H. The administration of the compounds was repeated in order to maintain the levels of oxysterols constant throughout the treatment. Compared with ethanol treatment, the oxysterol mixture decreased the surface expression of CD36 and CD204 scavenger receptors and reduced the amount of reactive oxygen species whereas it did not affect either cell viability or matrix metalloprotease-9 activity. Moreover, the oxysterol mixture increased the expression of both liver X receptor α and ATP-binding cassette transporter 1. An enhanced secretion of the immunoregulatory cytokine IL-10 accompanied these events. The results supported the hypothesis that the constant levels of oxysterols and, in particular, of 27-hydroxycholesterol stimulate macrophage polarization toward the M2 immunomodulatory functional phenotype, contributing to the stabilization of atherosclerotic plaques.
authors.affiliation: Department of Experimental Medicine, University of Genoa, via L. B. Alberti 2, Genoa, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Marengo
authors.affiliation: Department of Experimental Medicine, University of Genoa, via L. B. Alberti 2, Genoa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bellora
authors.affiliation: Department of Experimental Medicine, University of Genoa, via L. B. Alberti 2, Genoa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ricciarelli
authors.affiliation: Department of Experimental Medicine, University of Genoa, via L. B. Alberti 2, Genoa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: De Ciucis
authors.affiliation: Giannina Gaslini Institute, via G. Gaslini 5, Genoa, Italy.
authors.forename: AnnaLisa
authors.initials: A
authors.lastname: Furfaro
authors.affiliation: Department of Pharmacy, University of Genoa, Viale Cembrano 4, Genoa, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Leardi
authors.affiliation: Department of Experimental Medicine, University of Genoa, via L. B. Alberti 2, Genoa, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Colla
authors.affiliation: Department of Internal Medicine, University of Genoa, Viale Benedetto XV 6, Genoa, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Pacini
authors.affiliation: Department of Experimental Medicine, University of Genoa, via L. B. Alberti 2, Genoa, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Traverso
authors.affiliation: Department of Experimental Medicine, University of Genoa, via L. B. Alberti 2, Genoa, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.affiliation: Department of Experimental Medicine, University of Genoa, via L. B. Alberti 2, Genoa, Italy.
authors.forename: Maria Adelaide
authors.initials: MA
authors.lastname: Pronzato
authors.affiliation: Department of Experimental Medicine, University of Genoa, via L. B. Alberti 2, Genoa, Italy.|Giannina Gaslini Institute, via G. Gaslini 5, Genoa, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bottino
authors.affiliation: Department of Experimental Medicine, University of Genoa, via L. B. Alberti 2, Genoa, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Domenicotti
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018955:CD36 Antigens / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000008:administration & dosage / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage; D006801:Humans; D006888:Hydroxycholesterols / Q000008:administration & dosage*; D016753:Interleukin-10 / Q000378:metabolism; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009000:Monocytes / Q000187:drug effects; D057093:Orphan Nuclear Receptors / Q000096:biosynthesis; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D018955:CD36 Antigens; D006888:Hydroxycholesterols; C508609:IL10 protein, human; D000071518:Liver X Receptors; C495139:MSR1 protein, human; D057093:Orphan Nuclear Receptors; D017382:Reactive Oxygen Species; D051117:Scavenger Receptors, Class A; D016753:Interleukin-10; D000431:Ethanol; C076996:27-hydroxycholesterol; D002784:Cholesterol; D020780:Matrix Metalloproteinase 9
keywords: 27-hydroxycholesterol; atherosclerosis; cholesterol; macrophage polarization; oxysterols