Inhibition of Aerobic Glycolysis Promotes Neutrophil to Influx to the Infectious Site Via CXCR2 in Sepsis.
发布时间：2021-06-02
点击次数：
影响因子：2.96
发表刊物：Shock
关键字：2-deoxyglucose, G protein-coupled receptor kinase-2, immune metabolism, mice
摘要：Recent evidences suggest that metabolic reprogramming plays an important role in the regulation of innate inflammatory response; however, the specific mechanism is unclear. In this study, we found that glycolytic inhibitor 2-deoxyglucose (2-DG) significantly improved the survival rate in cecal ligation and puncture (CLP)-induced septic mice. 2-DG-treated mice developed increased neutrophil migration to the infectious site and more efficient bacterial clearance than untreated mice. 2-DG reversed the down-regulation of chemokine receptor 2 (CXCR2) and the impaired chemotaxis induced by CLP in mice or lipopolysaccharides (LPS) in human neutrophils. Furthermore, 2-DG reversed the down-regulation of CXCR2 in neutrophils by decreasing the expression of G protein-coupled receptor kinase-2 (GRK2), a serin-threonine protein kinase that mediated the internalization of chemokine receptors, which was induced via the inhibition of extracellular regulated protein kinases (ERK) phosphorylation and the promotion of P38 phosphorylation. Finally, SB225002, a CXCR2 antagonist, partially blocked the protective effects of 2-DG in sepsis. Together, we found a novel mechanism for the migration of neutrophils regulated by metabolism and suggested that aerobic glycolysis might be a potential target of intervention in sepsis.
合写作者：Huan Chen,Tao Li,Huafei Deng,Ke Liu,Meidong Liu,Sipin Tan,Zihui Xiao
第一作者：Chuyi Tan,Jia Gu
论文类型：基础研究
通讯作者：Huali Zhang(通讯作者),Xianzhong Xiao
学科门类：医学
一级学科：基础医学
期号：2020 Jan;53(1):114-123
是否译文：否
发表时间：2019-02-19
收录刊物：SCI