Abstract
Macrophages are polarized into different phenotypes depending on tissue microenvironment where they reside. In obesity-associated inflammation, M1-type macrophages are predominant in the inflamed tissue, exerting pro-inflammatory responses. Our previous studies demonstrate that blackcurrant consumption attenuates hepatic inflammation and lipopolysaccharide-stimulated inflammatory responses of splenocytes in obese mice. In this study, we determined whether blackcurrant modulates macrophage phenotypes to exert its anti-inflammatory action. Mouse bone marrow-derived macrophages (BMDM) and human THP-1 macrophages were polarized into M1 macrophages in the presence or absence of blackcurrant extract (BCE). BCE repressed M1 polarization of both murine and human macrophages. Also, to gain insight into the role of blackcurrant metabolites produced in vivo in the regulation of macrophage phenotypes, BMDM were treated with serum obtained from lean or obese mice fed blackcurrant. While serum from lean mice fed blackcurrant did not exert either anti-inflammatory actions or suppressive effects on M1 polarization, serum from obese mice fed blackcurrant reduced the expression of pro-inflammatory genes in BMDM. Our data demonstrate that BCE suppresses M1 polarization, with reduced pro-inflammatory responses. Moreover, this study suggests that blackcurrant metabolites may not exert their anti-inflammatory effect directly by altering macrophage phenotypes, but possibly by inhibiting the production of obesity-associated inflammatory factors.
Highlights
Macrophages are a heterogeneous population of immune cells that are distributed in all organs and play a crucial role in tissue homeostasis and host defense [1]
We further investigated whether blackcurrant can modulate macrophage phenotypes to exert its anti-inflammatory actions with a primary focus on the role of blackcurrant in the regulation of macrophage polarization in vitro, utilizing both mouse and human macrophages
As macrophages play a major role in inflammation, we determined whether blackcurrant exerts its anti-inflammatory actions via suppressing inflammatory responses in macrophages using polyphenol-rich blackcurrant extract (BCE)
Summary
Macrophages are a heterogeneous population of immune cells that are distributed in all organs and play a crucial role in tissue homeostasis and host defense [1]. Macrophages are functionally plastic in response to inflammatory cues from microbial products, damaged tissues, and activated lymphocytes [2,3]. The functional change or adaptation of macrophages in response to stimuli is referred to as macrophage polarization [4]. M1 macrophages produce pro-inflammatory cytokines, e.g., TNF, IL-1β, IL-12, and IL-6, and reactive oxygen species (ROS) [5,6]. M2 macrophages are specialized to produce immune-modulatory and reparative mediators such as IL-10, transforming growth factor β (TGFβ), IL-4, and IL-13, and to clear apoptotic cells due to their high phagocytosis capacity [7]
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