title: Resveratrol ameliorates LPS-induced acute lung injury via NLRP3 inflammasome modulation.
abstract: NLRP3 inflammasome plays a pivotal role in the development of acute lung injury (ALI), accelerating IL-1β and IL-18 release and inducing lung inflammation. Resveratrol, a natural phytoalexin, has anti-inflammatory properties via inhibition of oxidation, leukocyte priming, and production of inflammatory mediators. In this study, we aimed to investigate the effect of resveratrol on NLRP3 inflammasome in lipopolysaccharide-induced ALI. Mice were intratracheally instilled with 3mg/kg lipopolysaccharide (LPS) to induce ALI. Resveratrol treatment alleviated the LPS-induced lung pathological damage, lung edema and neutrophil infiltration. In addition, resveratrol reversed the LPS-mediated elevation of IL-1β and IL-18 level in the BAL fluids. In lung tissue, resveratrol also inhibited the LPS-induced NLRP3, ASC, caspase-1 mRNA and protein expression, and NLRP3 inflammasome activation. Moreover, resveratrol administration not only suppressed the NF-κB p65 nuclear translocation, NF-κB activity and ROS production in the LPS-treated mice, but also inhibited the LPS-induced thioredoxin-interacting protein (TXNIP) protein expression and interaction of TXNIP-NLRP3 in lung tissue. Meanwhile, resveratrol obviously induced SIRT1 mRNA and protein expression in the LPS-challenged mice. Taken together, our study suggests that resveratrol protects against LPS-induced lung injury by NLRP3 inflammasome inhibition. These findings further suggest that resveratrol may be of great value in the treatment of ALI and a potential and an effective pharmacological agent for inflammasome-relevant diseases.
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Kang
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Fei
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Gong
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Cao
authors.affiliation: The Key Hepatosplenic Surgery Laboratory, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Shangha
authors.initials: S
authors.lastname: Pan
authors.affiliation: Department of Pediatrics, Children's Hospital of Harbin City, Harbin, China.
authors.forename: Mingran
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of ICU, The First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: mingyan1970@126.com.
authors.forename: Mingyan
authors.initials: M
authors.lastname: Zhao
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D058847:Inflammasomes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011897:Random Allocation; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D058847:Inflammasomes; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D013267:Stilbenes; D000077185:Resveratrol
keywords: Acute lung injury; Lipopolysaccharide; NLRP3 inflammasome; Resveratrol