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Experimental gerontology

IF: 3.9
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AMPK as a potential pharmacological target for alleviating LPS-induced acute lung injury partly via NLRC4 inflammasome pathway inhibition

Published:1 October 2019 DOI:
Yuting He , Kan Xu , Yao Wang , Xin Chao , Bing'er Xu , Jiayu Wu , Jiping Shen , Weiying Ren , Yu Hu

Abstract

Old people are spectacularly susceptible to acute lung injury (ALI) and the accompanying complications. An acute aggravated inflammatory response is a characteristic feature of ALI, and inflammasomes play a critical role in the inflammatory response. Metformin has been shown to be an effective anti-inflammatory agent in ALI. However, the mechanism of this regulation still remains poorly understood. In this study, 18- to 19-month-old male mice were treated by intratracheal instillation of lipopolysaccharide (LPS) or PBS with or without metformin pretreatment. We found that the metformin pretreatment alleviated the lung injury and decreased the levels of TNF-a, IL-1β and IL-6 in the bronchoalveolar lavage fluid (BALF) and in lung tissues, as well as the levels of NLRP3, NLRC4 and cleaved caspase-1 associated with LPS-induced ALI in old mice. Furthermore, the in vitro study showed metformin dose-dependently suppressed NLRC4 inflammasome expression. Metformin activated AMPK by phosphorylation; thus, we investigated the role of AMPK in NLRC4 activation. The results demonstrated that the efficacy of metformin was reduced when using the AMPK pharmacological inhibitor compound C or AMPKα1 expression was knocked down in RAW 264.7 cells. In conclusion, our data indicated that metformin may inhibit NLRC4 inflammasome activation in LPS-induced ALI in old mice through AMPK signaling, and further understanding of the AMPK/NLRC4 axis may provide a novel therapeutic strategy for LPS-induced ALI in the future.

Substances (12)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Metformin hydrochloride 1115-70-4 C4H12ClN5 1000 suppliers $5.00-$1800.00
Metformin hydrochloride 1115-70-4 C4H12ClN5 1000 suppliers $5.00-$1800.00
Metformin hydrochloride 1115-70-4 C4H12ClN5 1000 suppliers $5.00-$1800.00
Metformin hydrochloride 1115-70-4 C4H12ClN5 1000 suppliers $5.00-$1800.00
6-[4-(2-PIPERIDIN-1-YLETHOXY)PHENYL]-3-PYRIDIN-4-YLPYRAZOLO[1,5-A]PYRIMIDINE 866405-64-3 C24H25N5O 267 suppliers $8.00-$2347.00
6-[4-(2-PIPERIDIN-1-YLETHOXY)PHENYL]-3-PYRIDIN-4-YLPYRAZOLO[1,5-A]PYRIMIDINE 866405-64-3 C24H25N5O 267 suppliers $8.00-$2347.00
6-[4-(2-PIPERIDIN-1-YLETHOXY)PHENYL]-3-PYRIDIN-4-YLPYRAZOLO[1,5-A]PYRIMIDINE 866405-64-3 C24H25N5O 267 suppliers $8.00-$2347.00
6-[4-(2-PIPERIDIN-1-YLETHOXY)PHENYL]-3-PYRIDIN-4-YLPYRAZOLO[1,5-A]PYRIMIDINE 866405-64-3 C24H25N5O 267 suppliers $8.00-$2347.00
Metformin HCl 1115-70-4 - Inquiry
Metformin HCl 1115-70-4 - Inquiry

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