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Inhibition of glycolysis alleviates lipopolysaccharide‐induced acute lung injury in a mouse model
Author(s) -
Zhong WenJing,
Yang HuiHui,
Guan XinXin,
Xiong JianBing,
Sun ChenChen,
Zhang ChenYu,
Luo XiaoQin,
Zhang YanFeng,
Zhang Jun,
Duan JiaXi,
Zhou Yong,
Guan ChaXiang
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27261
Subject(s) - proinflammatory cytokine , glycolysis , lipopolysaccharide , anaerobic glycolysis , inflammasome , inflammation , tumor necrosis factor alpha , chemistry , immunology , medicine , biochemistry , metabolism
Gluconic metabolic reprogramming, immune response, and inflammation are intimately linked. Glycolysis involves in the pathologic progress in acute and chronic inflammatory diseases. However, the involvement of glycolysis in the acute lung injury (ALI) is still unclear. This study investigated the role of glycolysis in an animal model of ALI. First, we found that lactate content in serum was remarkably increased in ALI patients and a murine model induced by intratracheal administration of lipopolysaccharide (LPS). The key proteins involving in glycolysis were robustly elevated, including HK2 , PKM2 , and HIF‐1α . Intriguingly, inhibition of glycolysis by 2‐deoxyglucose (2‐DG) pronouncedly attenuated the lung tissue pathological injury, accumulation of neutrophil, oxidative stress, expression of proinflammatory factors in the lung of ALI mice induced by LPS. The 2‐DG treatment also strongly suppressed the activation of the NOD‐like receptor (NLR) family and pyrin domain‐containing protein 3 (NLRP3) inflammasome. Furthermore, we investigated the role of glycolysis in the inflammatory response of primary murine macrophages activated by LPS in vitro. We found that the 2‐DG treatment remarkably reduced the expression of proinflammatory factors induced by LPS, including tumor necrosis factor‐α messenger RNA (mRNA), pro‐interleukin (IL)‐1β mRNA, pro‐IL‐18 mRNA, NLRP3 mRNA, caspase‐1 mRNA, and IL‐1β protein. Altogether, these data provide a novel link between gluconic metabolism reprogramming and uncontrolled inflammatory response in ALI. This study suggests glycolytic inhibition as an effective anti‐inflammatory strategy in treating ALI.