title: Pomegranate juice polyphenols induce a phenotypic switch in macrophage polarization favoring a M2 anti-inflammatory state.
abstract: It was documented that pomegranate has anti-inflammatory effects. In this study, we investigated a direct effect of pomegranate juice (PJ) and its polyphenols on macrophage inflammatory phenotype. In vitro, PJ and its major polyphenols dose-dependently attenuated macrophage response to M1 proinflammatory activation in J774.A1 macrophage-like cell line. This was evidenced by a significant decrease in TNFα and IL-6 secretion in response to stimulation by IFNγ and Lipopolysaccharide. In addition, PJ and punicalagin dose-dependently promoted the macrophages toward a M2 anti-inflammatory phenotype, as determined by a significant increase in the spontaneous secretion of IL-10. In mice, supplementation with dietary PJ substantially inhibited the M2 to M1 macrophage phenotypic shift associated with age, toward a favorable anti-inflammatory M2 phenotype. This effect was also reflected in the mice atherosclerotic plaques, as evaluated by the distinct expression of arginase isoforms. PJ consumption inhibited the increment of arginase II (Arg II, M1) mRNA expression during aging, and maintained the levels of Arg I (M2) expression similar to those in young mice aorta. This study demonstrates, for the first time, that pomegranate polyphenols directly suppress macrophage inflammatory responses and promote M1 to M2 switch in macrophage phenotype. Furthermore, this study indicates that PJ consumption may inhibit the progressive proinflammatory state in the aorta along atherosclerosis development with aging, due to a switch in macrophage phenotype from proinflammatory M1 to anti-inflammatory M2.
authors: The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, and Rambam Medical Center, Haifa, Israel.
authors: Saar
authors: S
authors: Aharoni
authors: Yoni
authors: Y
authors: Lati
authors: Michael
authors: M
authors: Aviram
authors: Bianca
authors: B
authors: Fuhrman
mesh_terms: D000375:Aging / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D001119:Arginase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D001628:Beverages; D002460:Cell Line; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology; D016753:Interleukin-10 / Q000819:agonists / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D029561:Lythraceae / Q000737:chemistry*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D018384:Oxidative Stress; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C556062:IL10 protein, mouse; D008070:Lipopolysaccharides; D016753:Interleukin-10; D007371:Interferon-gamma; C544448:Arg1 protein, mouse; C481673:Arg2 protein, mouse; D001119:Arginase
keywords: M1/M2 activation; inflammation; macrophages; polyphenols; pomegranate juice