title: Suppression of RAGE and TLR9 by Ketamine Contributes to Attenuation of Lipopolysaccharide-Induced Acute Lung Injury.
abstract: The present study aimed to investigate the protective role of ketamine in lipopolysaccharide (LPS)-induced acute lung injury (ALI) by the inhibition of the receptor for advanced glycation end products (RAGE) and toll-like receptor 9 (TLR9). ALI was induced in rats by intratracheal instillation of LPS (5 mg/kg), and ketamine (5, 7.5, and 10 mg/kg) was injected intraperitoneally 1 h after LPS administration. Meanwhile, A549 alveolar epithelial cells were incubated with LPS in the presence or absence of ketamine. After 24 h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Ketamine posttreatment at doses of 5, 7.5, and 10 mg/kg decreased LPS-induced evident lung histopathological changes, lung wet-to-dry weight ratio, and lung myeloperoxidase activity. In addition, posttreatment with ketamine-inhibited inflammatory cells and inflammatory mediators including tumor necrosis factor-α, interleukin-6, and high-mobility group box 1 in BALF. Furthermore, we demonstrated that ketamine-inhibited LPS-induced RAGE and TLR9 protein up-expressions and the phosphorylation of I-κB-α and nuclear factor-κB (NF-κB) p65 in vivo and in vitro. The results presented here suggest that the protective mechanism of ketamine may be attributed partly to decreased production of inflammatory mediators through the inhibition of RAGE/TLR9-NF-κB pathway.
authors.affiliation: a Department of Anesthesiology , Shaanxi Provincial People's Hospital , Xi'an , Shaanxi , China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Yang
authors.affiliation: a Department of Anesthesiology , Shaanxi Provincial People's Hospital , Xi'an , Shaanxi , China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: Song
authors.affiliation: a Department of Anesthesiology , Shaanxi Provincial People's Hospital , Xi'an , Shaanxi , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism / Q000517:prevention & control*; D000778:Anesthetics, Dissociative / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004353:Drug Evaluation, Preclinical; D007649:Ketamine / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D008297:Male; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: C000593874:Ager protein, rat; D000778:Anesthetics, Dissociative; D008070:Lipopolysaccharides; D000067759:Receptor for Advanced Glycation End Products; C489640:Tlr9 protein, rat; D051217:Toll-Like Receptor 9; D007649:Ketamine
keywords: acute lung injury; ketamine; lipopolysaccharide; the receptor for advanced glycation end products; toll-like receptor 9