title: Isoflurane attenuates lipopolysaccharide-induced acute lung injury by inhibiting ROS-mediated NLRP3 inflammasome activation.
abstract: Nucleotide-binding domains and leucine-rich repeat (NLR) pyrin domains containing 3 (NLRP3) inflammasome are highly involved in the pathogenesis of acute lung injury (ALI) wherein alveolar macrophages (AMs) play a crucial role. Isoflurane (ISO) has been shown to attenuate ALI. However, the inhibitory effects of ISO on NLRP3 activation in lipopolysaccharide (LPS)-induced ALI remain unknown. Here, we showed that 1.4% ISO post-treatment reduced LPS-induced body weight loss, pulmonary histopathological injury, edema, and vascular permeability in rats. ISO attenuated LPS-triggered inflammation, as evidenced by reductions in the number of total cells, neutrophils, and macrophages, and the release of IL-1β and IL-18 in the bronchoalveolar lavage fluid. ISO treatment decreased the myeloperoxidase activity, F4/80-positive cells, and the mRNA expression of IL-1β and IL-18 in the lung tissues of LPS-treated rats. Mechanistically, ISO reduced NLRP3 activation and caspase-1 activity in a reactive oxygen species (ROS)-dependent manner. An in vitro study that ISO inhibited LPS-induced AM activation partly confirmed in vivo findings. Overall, these results indicate that ISO post-conditioning alleviated LPS-induced ALI possibly by inhibiting ROS-mediated NLRP3 inflammasome activation.
authors.affiliation: Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University Nanjing 210009, Jiangsu, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yin
authors.affiliation: Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University Nanjing 210009, Jiangsu, China.
authors.forename: Zhendan
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University Nanjing 210009, Jiangsu, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University Nanjing 210009, Jiangsu, China.
authors.forename: Jiangyan
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University Nanjing 210009, Jiangsu, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University Nanjing 210009, Jiangsu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University Nanjing 210009, Jiangsu, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University Nanjing 210009, Jiangsu, China.
authors.forename: Xinjiang
authors.initials: X
authors.lastname: Lu
keywords: Acute lung injury; isoflurane; lipopolysaccharide; nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3; reactive oxygen species