The Antioxidant Procyanidin Reduces Reactive Oxygen Species Signaling in Macrophages and Ameliorates Experimental Colitis in Mice.

Lu Chen,Xuefeng Wu,Qianqian Meng,Qian You,Liang Hu,Qiang Xu,Wentao Liu,Jian Gao

doi:10.3389/fimmu.2017.01910

Abstract

Management of inflammatory bowel disease (IBD) is a real clinical challenge. Despite intense investigation, the mechanisms of IBD remain substantially unidentified. Some inflammatory conditions, such as matrix metalloproteinases (MMPs) and the nuclear factor-κB (NF-κB) and NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathways, are reported to contribute to the development and maintenance of IBD. Regulation of their common upstream signaling, that is, reactive oxygen species (ROS), may be important to control the progression of IBD. In the present study, we found that procyanidin, a powerful antioxidation flavonoid, has a significant effect on ROS clearance on THP-1 macrophages after lipopolysaccharide (LPS) or LPS-combined adenosine triphosphate stimulation, thus downregulating MMP9 expression, suppressing NF-κB signaling, and interrupting the formation of the NLRP3 inflammasome. Moreover, our in vivo data showed that procyanidin attenuated Dextran sulfate sodium-induced experimental colitis in a dose-dependent fashion by suppressing the expression of MMP9, NF-κB, and NLRP3 inflammasome signaling in colonic tissues in mice. Overall, our results suggested that targeting ROS could be a potential therapeutic choice for colonic inflammation.

Highlights

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is characterized by chronic, relapsing inflammation that significantly lowers the quality of life of patients and even increases the risk of colon cancer [1, 2]
We examined the anti-inflammatory effect of procyanidin in dextran sulfate sodium (DSS)-induced colitis and found that procyanidin decreased the generation of Reactive oxygen species (ROS), inhibiting the expression of MMP9, nuclear factor-κB (NF-κB), and formation of the NOD-like receptor protein 3 (NLRP3) inflammasome
THP-1 cells were differentiated to macrophages by cultured with Phorbolmyristate acetate (PMA) (500 nM) for 3 h, and single LPS (100 ng/ml) or LPS (100 ng/ml) combined with adenosine triphosphate (ATP) (5 mM) stimulation—two classic methods of inducing activation of TLR4-NF-κB and the NLRP3 inflammasome, respectively—were applied to mimic the inflammatory condition in THP-1 cells

Summary

Introduction

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is characterized by chronic, relapsing inflammation that significantly lowers the quality of life of patients and even increases the risk of colon cancer [1, 2]. It is widely accepted that disruption of the epithelial barrier triggers invasion of bacterial antigens into the mucosal layer, resulting in activation of the mucosal immune response [3]. During this process, macrophages play a key role because they can release large amounts of proinflammatory cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α, which exacerbate the severity of the inflammation condition and colitis [4]. There is substantial evidence that ROS have a strong correlation with colitis [6] and are over-produced in the colon of

Methods

Results

Conclusion