Galectin-1 ameliorates lipopolysaccharide-induced acute lung injury via AMPK-Nrf2 pathway in mice

• Published in: Free radical biology & medicine Vol. 146; pp. 222 - 233
• Main Authors: Huang, Xiao-Ting, Liu, Wei, Zhou, Yong, Sun, Mei, Yang, Hui-Hui, Zhang, Chen-Yu, Tang, Si-Yuan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2020
• Subjects: Acute lung injury; AMPK; Galectin-1; Inflammation; Nrf-2; Oxidative stress; Acute lung injury; Oxidative stress; Galectin-1; AMPK; Inflammation; Nrf-2
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2019.11.011

Inflammation and oxidative stress contribute to the progression of acute lung injury (ALI). Galectin-1 (Gal-1) has important anti-inflammatory properties in renal ischemia-reperfusion injury, arthritis, uveitis, and hepatitis. However, whether Gal-1 could protect against ALI is still poorly elucidated. The current study aimed to investigate the protective effects of Gal-1 against lipopolysaccharide (LPS)-induced ALI and the underlying mechanisms. Accordingly, we found that pretreatment with Gal-1 attenuated the lung tissue injury induced by LPS, with the recovery of lung function, protecting against the production of pro-inflammatory cytokines and oxidative stress. We also confirmed the therapeutic potential of Gal-1 on the survival rate of LPS-challenged mice. In vitro studies demonstrated the protective effects of exogenous Gal-1 through downregulating pro-inflammatory cytokines release and oxidative stress in primary macrophages challenged by LPS. In addition, Gal-1 suppressed TXNIP-NLRP3 inflammasome activation in ALI mice and LPS-treated primary macrophages partly through directly binding to the NLRP3 protein. Gal-1 alleviated LPS-induced lung injury via activation of Nrf-2, which may be associated with AMPK phosphorylation. Collectively, our experimental results firstly provided the support that Gal-1 effectively protected against LPS-induced ALI via suppression of inflammation response and oxidative stress, which were largely dependent on the upregulation of the Nrf2 pathway via phosphorylation of AMPK. These results suggest that Gal-1 could be a valuable therapeutic candidate in the treatment of ALI. [Display omitted] •Galectin-1 ameliorates LPS-induced acute lung injury in mice.•Galectin-1 attenuates LPS-induced NLRP3 inflammation activation and oxidative stress in primary macrophages.•Galectin-1 alleviates LPS-induced injury via AMPK/Nrf-2 pathway.