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Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
Pomegranate juice polyphenols induce a phenotypic switch in macrophage polarization favoring a M2 anti-inflammatory
Saar Aharoni1, Yoni Lati, Michael Aviram
1The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, and Rambam Medical Center, Haifa, Israel.
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.
Insights
Pomegranate juice (PJ) and its polyphenols directly reduce pro-inflammatory macrophage responses and promote anti-inflammatory phenotypes. PJ consumption may combat age-related inflammation and atherosclerosis by shifting macrophage polarization.
Area of Science:
- Immunology
- Nutritional Science
- Cell Biology
Background:
- Pomegranate is known for anti-inflammatory properties.
- Macrophage polarization (M1 pro-inflammatory, M2 anti-inflammatory) plays a key role in inflammation and diseases like atherosclerosis.
- The direct impact of pomegranate on macrophage phenotype requires further investigation.
Purpose of the Study:
- To investigate the direct effects of pomegranate juice (PJ) and its polyphenols on macrophage inflammatory phenotype.
- To determine if PJ can modulate the M1/M2 macrophage balance in vitro and in vivo.
- To explore the potential of PJ in mitigating age-related inflammation and atherosclerosis.
Main Methods:
- In vitro studies using J774.A1 macrophage-like cell line treated with PJ and its polyphenols.
- Measurement of pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-10) cytokine secretion.
- In vivo studies in mice supplemented with dietary PJ, analyzing macrophage phenotype in aorta and atherosclerotic plaques.
- Assessment of arginase isoform (Arg I, Arg II) mRNA expression in aortic tissue.
Main Results:
- PJ and its polyphenols dose-dependently attenuated M1 pro-inflammatory activation and decreased TNFα and IL-6 secretion.
- PJ and punicalagin promoted an M2 anti-inflammatory phenotype, evidenced by increased IL-10 secretion.
- Dietary PJ supplementation shifted macrophages towards an M2 phenotype in aging mice, reducing M1 markers (Arg II) and maintaining M2 markers (Arg I) in the aorta.
- These changes were reflected in atherosclerotic plaques, suggesting reduced inflammation.
Conclusions:
- Pomegranate polyphenols directly suppress macrophage inflammatory responses and promote a shift from M1 to M2 phenotype.
- Pomegranate juice consumption may inhibit the progression of atherosclerosis and age-related inflammation by modulating macrophage polarization.
- This study provides novel insights into the immunomodulatory mechanisms of pomegranate in the context of aging and cardiovascular health.
