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

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.

A GLP-1 Analog Liraglutide Reduces Intimal Hyperplasia After Coronary Stent Implantation via Regulation of Glycemic Variability and NLRP3 Inflammasome/IL-10 Signaling in Diabetic Swine

“…These observations were supported by previous studies (Rakipovski et al, 2018;Zhu et al, 2018;Sharma et al, 2018;Bruen et al, 2019). The protective effect of the GLP-1 receptor agonist liraglutide on blood vessels occurs via GLP-1 receptor-dependent or independent signals (Zhong et al, 2019). In the in vitro study, liraglutide treatment significantly decreased NLRP3 and increased IL-10 protein expression compared with that of the HG group.…”

COX‐2/sEH dual inhibitor PTUPB alleviates bleomycin‐induced pulmonary fibrosis in mice via inhibiting senescence

“…The mice were sacrificed under anesthesia on the 21st day after the BLM injection. All surgeries were performed under anesthesia with an intraperitoneal injection of sodium pentobarbital (80 mg·kg −1 ) .…”

“…The mRNA levels were detected with SYBR using real‐time PCR system (CFX96 Touch™; Bio‐Rad, Hercules, CA, USA). The fold change of gene expression was detected using the 2 −ΔΔCT method according to our previous study , while the profile of CYPs in the lung was calculated using the 2 −ΔCT method. Primers for real‐time PCR are listed in Table .…”

Prolonged Exposure to Traffic-related Particulate Matter Showed Distinct Molecular Mechanisms of Lung Injury in Rats

“…Increased oxidative phosphorylation was observed in both 3M-PM 1 and 3M-GAS groups which may imply impaired mitochondrial functions, higher oxidative stress (48) and probably a compensation of metabolic shifting from glycolysis to pentose phosphate pathway (49). Glycolysis was reported to worsen infection related-pulmonary brosis (50), and inhibition of glycolysis would attenuate the injury by suppressing in ammation and apoptosis (51,52). Concurrently, our model showed negative regulation of glycolysis/gluconeogenesis in chronic PM 1 -exposed rats, suggesting a potential mechanism to limit lung injury.…”