sDR5-Fc inhibits macrophage M1 polarization by blocking the glycolysis  

作　　者：Guang-Yao ZHAI Shu-Yan QIE Qian-Yun GUO Yue QI Yu-Jie ZHOU 

机构地区：[1]Department of Cardiology,Beijing Anzhen Hospital,Capital Medical University,Beijing Institute of Heart Lung and Blood Vessel Disease,Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease,Clinical Center for Coronary Heart Disease,Capital Medical University,Beijing,China [2]Department of Rehabilitation,Beijing Rehabilitation Hospital of Capital Medical University,Beijing,China [3]Department of Epidemiology,Beijing Anzhen Hospital,Capital Medical University,Beijing Institute of Heart Lung and Blood Vessel Disease,Beijing,China

出　　处：《Journal of Geriatric Cardiology》2021年第4期271-280,共10页老年心脏病学杂志（英文版）

基　　金：supported by the National Natural Science Foundation of Beijing, China (No.7212027 & No.7214223);National Key Research and Development Program of China (2017YFC0908800);the Beijing Municipal Health Commission (PXM2020_026272_000002 & PXM2020_026272_000014)。

摘　　要：BACKGROUND M1 polarization of macrophages is an important pathological process in myocardial ischemia reperfusion injury, which is the major obstacle for the treatment of acute myocardial infarction. Currently, the strategies and mechanisms of inhibiting M1 polarization are poorly explored. This study aims to investigate the role of soluble death receptor 5-Fc(s DR5-Fc) in regulating M1 polarization of macrophages under extreme conditions and explore the mechanisms from the aspect of glycolysis.METHODS Extreme conditions were induced in RAW264.7 cells. Real-time quantitative polymerase chain reaction and western blot were used to detect the expression of m RNA and proteins, respectively. Cell counting kit-8 was used to investigate the proliferation activity of cells. Expression levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay.RESULTS We found that s DR5-Fc rescues the proliferation of macrophages under extreme conditions, including nutrition deficiency, excessive peroxide, and ultraviolet irradiation. In addition, administration of s DR5-Fc inhibits the M1 polarization of macrophages induced by lipopolysaccharide(LPS) and interferon-gamma(IFN-γ), as the expression of M1 polarization markers CD86, CXC motif chemokine ligand 10, matrix metalloproteinase 9, and tumor necrosis factor-α, as well as the secretion of inflammatory factors interleukin(IL)-1β and IL-6, were significantly decreased. By further investigation of the mechanisms, the results showed that s DR5-Fc can recover the LPS and IFN-γ induced p H reduction, lactic acid elevation, and increased expression of hexokinase 2 and glucose transporter 1, which were markers of glycolysis in macrophages.CONCLUSIONS s DR5-Fc inhibits the M1 polarization of macrophages by blocking the glycolysis, which provides a new direction for the development of strategies in the treatment of myocardial ischemia reperfusion injury.

关 键 词：RNA IFN sDR5-Fc inhibits macrophage M1 polarization by blocking the glycolysis 

分 类 号：R542.22[医药卫生—心血管疾病]