Inhibition of glycolysis alleviates lipopolysaccharide-induced acute lung injury in a mouse model - PubMed (original) (raw)

. 2019 Apr;234(4):4641-4654.

doi: 10.1002/jcp.27261. Epub 2018 Sep 7.

Hui-Hui Yang 1, Xin-Xin Guan 1, Jian-Bing Xiong 1, Chen-Chen Sun 1, Chen-Yu Zhang 1, Xiao-Qin Luo 1, Yan-Feng Zhang 1, Jun Zhang 2, Jia-Xi Duan 3, Yong Zhou 1, Cha-Xiang Guan 1

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Inhibition of glycolysis alleviates lipopolysaccharide-induced acute lung injury in a mouse model

Wen-Jing Zhong et al. J Cell Physiol. 2019 Apr.

Abstract

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.

Keywords: 2-deoxyglucose; NLRP3 inflammasome; acute lung injury; glycolysis; macrophages.

© 2018 Wiley Periodicals, Inc.

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