PMID- 30829852
OWN - NLM
STAT- MEDLINE
DCOM- 20210201
LR  - 20210213
IS  - 1540-0514 (Electronic)
IS  - 1073-2322 (Linking)
VI  - 53
IP  - 1
DP  - 2020 Jan
TI  - Inhibition of Aerobic Glycolysis Promotes Neutrophil to Influx to the Infectious 
      Site Via CXCR2 in Sepsis.
PG  - 114-123
LID - 10.1097/SHK.0000000000001334 [doi]
AB  - 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.
FAU - Tan, Chuyi
AU  - Tan C
AD  - Key Laboratory of Sepsis Translational Medicine of Hunan, Department of 
      Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, 
      Hunan, China.
FAU - Gu, Jia
AU  - Gu J
FAU - Chen, Huan
AU  - Chen H
FAU - Li, Tao
AU  - Li T
FAU - Deng, Huafei
AU  - Deng H
FAU - Liu, Ke
AU  - Liu K
FAU - Liu, Meidong
AU  - Liu M
FAU - Tan, Sipin
AU  - Tan S
FAU - Xiao, Zihui
AU  - Xiao Z
FAU - Zhang, Huali
AU  - Zhang H
FAU - Xiao, Xianzhong
AU  - Xiao X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Shock
JT  - Shock (Augusta, Ga.)
JID - 9421564
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Phenylurea Compounds)
RN  - 0 (Receptors, Interleukin-8B)
RN  - 0 (SB 225002)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - EC 2.7.11.15 (GRK2 protein, mouse)
RN  - EC 2.7.11.16 (G-Protein-Coupled Receptor Kinase 2)
SB  - IM
MH  - Animals
MH  - Deoxyglucose/metabolism
MH  - G-Protein-Coupled Receptor Kinase 2/antagonists & inhibitors/*metabolism
MH  - Glycolysis/drug effects
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Neutrophils/drug effects/*metabolism
MH  - Phenylurea Compounds/pharmacology
MH  - Receptors, Interleukin-8B/*antagonists & inhibitors
EDAT- 2019/03/05 06:00
MHDA- 2021/02/02 06:00
CRDT- 2019/03/05 06:00
PHST- 2019/03/05 06:00 [pubmed]
PHST- 2021/02/02 06:00 [medline]
PHST- 2019/03/05 06:00 [entrez]
AID - 00024382-202001000-00015 [pii]
AID - 10.1097/SHK.0000000000001334 [doi]
PST - ppublish
SO  - Shock. 2020 Jan;53(1):114-123. doi: 10.1097/SHK.0000000000001334.