Pinosylvin Shifts Macrophage Polarization to Support Resolution of Inflammation.

Konsta Kivimäki,Tiina Leppänen,Katriina Vuolteenaho,Eeva Moilanen,Mari Hämäläinen

doi:10.3390/molecules26092772

Konsta Kivimäki, Tiina Leppänen + Show 3 more

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https://doi.org/10.3390/molecules26092772

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Abstract

Pinosylvin is a natural stilbenoid found particularly in Scots pine. Stilbenoids are a group of phenolic compounds identified as protective agents against pathogens for many plants. Stilbenoids also possess health-promoting properties in humans; for instance, they are anti-inflammatory through their suppressing action on proinflammatory M1-type macrophage activation. Macrophages respond to environmental changes by polarizing towards proinflammatory M1 phenotype in infection and inflammatory diseases, or towards anti-inflammatory M2 phenotype, mediating resolution of inflammation and repair. In the present study, we investigated the effects of pinosylvin on M2-type macrophage activation, aiming to test the hypothesis that pinosylvin could polarize macrophages from M1 to M2 phenotype to support resolution of inflammation. We used lipopolysaccharide (LPS) to induce M1 phenotype and interleukin-4 (IL-4) to induce M2 phenotype in J774 murine and U937 human macrophages, and we measured expression of M1 and M2-markers. Interestingly, along with inhibiting the expression of M1-type markers, pinosylvin had an enhancing effect on the M2-type activation, shown as an increased expression of arginase-1 (Arg-1) and mannose receptor C type 1 (MRC1) in murine macrophages, and C-C motif chemokine ligands 17 and 26 (CCL17 and CCL26) in human macrophages. In IL-4-treated macrophages, pinosylvin enhanced PPAR-γ expression but had no effect on STAT6 phosphorylation. The results show, for the first time, that pinosylvin shifts macrophage polarization from the pro-inflammatory M1 phenotype towards M2 phenotype, supporting resolution of inflammation and repair.

Highlights

Macrophages play a major role in the immune system, especially during infection and inflammation, and in healing and repair
We investigated the anti-inflammatory effects of the fairly unknown and inscrutable stilbenoid, pinosylvin, from the aspect of the pleiotropic immune cell macrophage
We hypothesized that pinosylvin could shift macrophage polarization towards the alternative M2 phenotype under inflammatory conditions

Summary

Introduction

Macrophages play a major role in the immune system, especially during infection and inflammation, and in healing and repair. They function as phagocytes that can eradicate micro-organisms and matrix debris. Activated, known as proinflammatory M1-type, macrophages functionally participate, especially during inflammation, in the elimination of pathogens by phagocytosis and in the signaling of other inflammatory and tissue cells through secreting pro-inflammatory cytokines and other mediators, such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP1), and nitric oxide (NO), which is produced in high amounts during inflammation by inducible nitric oxide synthase (iNOS) [1].

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