Impact Factor:2.96
Journal:Shock
Key Words:2-deoxyglucose, G protein-coupled receptor kinase-2, immune metabolism, mice
Abstract: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.
Co-author:Huan Chen,Tao Li,Huafei Deng,Ke Liu,Meidong Liu,Sipin Tan,Zihui Xiao
First Author:Chuyi Tan,Jia Gu
Indexed by:Unit Twenty Basic Research
Correspondence Author:Huali Zhang(通讯作者),Xianzhong Xiao
Discipline:Medicine
First-Level Discipline:Basic Medicine
Issue:2020 Jan;53(1):114-123
Translation or Not:no
Included Journals:SCI