Effect of Cocoa Polyphenolic Extract on Macrophage Polarization from Proinflammatory M1 to Anti-Inflammatory M2 State.

Laura Dugo,Marina Russo,Maria Giovanna Belluomo,Mauro Maccarrone,Chiara Fanali,Anna Maria Sardanelli,Francesco Cacciola

doi:10.1155/2017/6293740

Abstract

Polyphenols-rich cocoa has many beneficial effects on human health, such as anti-inflammatory effects. Macrophages function as control switches of the immune system, maintaining the balance between pro- and anti-inflammatory activities. We investigated the hypothesis that cocoa polyphenol extract may affect macrophage proinflammatory phenotype M1 by favoring an alternative M2 anti-inflammatory state on macrophages deriving from THP-1 cells. Chemical composition, total phenolic content, and antioxidant capacity of cocoa polyphenols extracted from roasted cocoa beans were determined. THP-1 cells were activated with both lipopolysaccharides and interferon-γ for M1 or with IL-4 for M2 switch, and specific cytokines were quantified. Cellular metabolism, through mitochondrial oxygen consumption, and ATP levels were evaluated. Here, we will show that cocoa polyphenolic extract attenuated in vitro inflammation decreasing M1 macrophage response as demonstrated by a significantly lowered secretion of proinflammatory cytokines. Moreover, treatment of M1 macrophages with cocoa polyphenols influences macrophage metabolism by promoting oxidative pathways, thus leading to a significant increase in O2 consumption by mitochondrial complexes as well as a higher production of ATP through oxidative phosphorylation. In conclusion, cocoa polyphenolic extract suppresses inflammation mediated by M1 phenotype and influences macrophage metabolism by promoting oxidative pathways and M2 polarization of active macrophages.

Highlights

Monocyte-derived macrophages play a crucial role in inflammation, host defense, and tissue repair [1, 2]
We investigated the hypothesis that cocoa polyphenol extract may affect macrophage proinflammatory phenotype M1 by favoring an alternative M2 anti-inflammatory state on macrophages deriving from THP-1 cells
For the first time, that cocoa extract dramatically inhibited the secretion of the proinflammatory cytokines TNF-α, IL-6, IL-1β, and IL-12 in INF-γ/LPS-stimulated macrophages of the same percentage by which it increased cell viability, compared to control

Summary

Introduction

Monocyte-derived macrophages play a crucial role in inflammation, host defense, and tissue repair [1, 2]. Macrophages have important pathogenic roles in many chronic diseases, such as asthma, inflammatory bowel disease, atherosclerosis, rheumatoid arthritis, and fibrosis [2,3,4]. Many studies have attempted to simulate the process of monocyte to macrophage differentiation in vitro, through the culture of monocytes with or without addition of different cytokines [5]. Phenotypic and functional flexibility is a key property of macrophages [6,7,8,9]. Over the last few years, considerable progress has been made toward characterization of epigenetic mechanisms, transcription, and posttranscriptional factors regulating macrophage polarization [10]. M1 activation is drived by the cytokine interferon- (IFN-) γ and the activation of Toll-like receptors (TLRs) by lipopolysaccharide (LPS), while M2 activation is triggered by interleukin- (IL-)

Methods

Results

Discussion

Conclusion