title: Resveratrol counteracts inflammation in human M1 and M2 macrophages upon challenge with 7-oxo-cholesterol: potential therapeutic implications in atherosclerosis.
abstract: the proinflammatory M1 subset and the anti-inflammatory M2 one. 7-oxo-cholesterol, the most abundant cholesterol autoxidation product within atherosclerotic plaque, is able to skew the M1/M2 balance towards a proinflammatory profile. In the present study, we explored the ability of the polyphenolic compound resveratrol to counteract the 7-oxo-cholesterol-triggered proinflammatory signaling in macrophages. Resveratrol-pretreated human monocyte-derived M1 and M2 macrophages were challenged with 7-oxo-cholesterol and analyzed for phenotype and endocytic ability by flow cytometry, for metalloproteinase- (MMP-) 2 and MMP-9 by gelatin zymography, and for cytokine, chemokine, and growth factor secretome by a multiplex immunoassay. We also investigated the NF-κB signaling pathway. In the M1 subset, resveratrol prevented the downregulation of CD16 and the upregulation of MMP-2 in response to 7-oxo-cholesterol, whereas in M2 macrophages it prevented the upregulation of CD14, MMP-2, and MMP-9 and the downregulation of endocytosis. Resveratrol prevented the upregulation of several proinflammatory and proangiogenic molecules in both subsets. We identified modulation of NF-κB as a potential mechanism implicated in 7-oxo-cholesterol and resveratrol effects. Our results strengthen previous findings on the immunomodulatory ability of resveratrol and highlight its role as potential therapeutic or preventive compound, to counteract the proatherogenic oxysterol signaling within atherosclerotic plaque.
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Brigitta
authors.identifier: 0000-0002-0575-4106
authors.initials: B
authors.lastname: Buttari
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Elisabetta
authors.identifier: 0000-0002-7261-8884
authors.initials: E
authors.lastname: Profumo
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Luca
authors.identifier: 0000-0002-5666-8312
authors.initials: L
authors.lastname: Segoni
authors.affiliation: Laboratory of Vascular Pathology, Istituto Dermopatico dell'Immacolata, IDI-IRCCS, 00167 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Arcangelo
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Rossi
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Facchiano
authors.affiliation: Department of Physiology and Pharmacology "Vittorio Erspamer", La Sapienza University of Rome, 00181 Rome, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Saso
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnology, Sapienza University of Rome, 04100 Latin, Italy.
authors.forename: Rita
authors.identifier: 0000-0002-7890-8524
authors.initials: R
authors.lastname: Businaro
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnology, Sapienza University of Rome, 04100 Latin, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Iuliano
authors.affiliation: Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Rachele
authors.initials: R
authors.lastname: Riganò
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007653:Ketocholesterols / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018925:Chemokines; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D007653:Ketocholesterols; D018950:Lipopolysaccharide Receptors; D016328:NF-kappa B; D017452:Receptors, IgG; D013267:Stilbenes; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C003001:7-ketocholesterol; D000077185:Resveratrol