title: 15-deoxy-Δ¹²,¹⁴-prostaglandin J₂ ameliorates endotoxin-induced acute lung injury in rats.
abstract: BACKGROUND
  A proinflammatory milieu emerging in the lung due to neutrophil accumulation and activation is a key in the pathogenesis of acute lung injury (ALI). 15-deoxy-Δ(12, 14)-prostaglandin J2 (15d-PGJ2), one of the terminal products of the cyclooxygenase-2 pathway, is known to be the endogenous ligand of peroxisome proliferator-activated receptor γ (PPAR-γ) with multiple physiological properties. Growing evidence indicates that 15d-PGJ2 has anti-inflammatory, antiproliferative, cytoprotective and pro-resolving effects. We investigated whether 15d-PGJ2 has a protective effect against endotoxin-induced acute lung injury in rats.
  
  
  METHODS
  Twenty-four male Wistar rats were randomly assigned into four groups (n = 6 per group): sham+vehicle group, sham+15d-PGJ2 group, LPS+vehicle group, and LPS+15d-PGJ2 group. The rats were given either lipopolysaccharide (LPS, 6 mg/kg intravenously) or saline, and pretreated with 15d-PGJ2 (0.3 mg/kg intravenously) or its vehicle (dimethyl sulphoxide) 30 minutes before LPS. Histological alterations, wet/dry weight (W/D) ratio and myeloperoxidase (MPO) activity as well as tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant-1 (CINC-1) levels were determined in lung tissues four hours after LPS injection. Immunohistochemical analysis for intercellular adhesion molecule-1 (ICAM-1) expression and Western blotting analysis for nuclear factor (NF)-κB p65 translocation and IκBα protein levels were also studied.
  
  
  RESULTS
  15d-PGJ2 pretreatment significantly attenuated LPS-induced lung injury, and reduced the increased W/D ratio, MPO activity, TNF-α, CINC-1 levels, and ICAM-1 expression in the lung. 15d-PGJ2 also suppressed the nuclear NF-κB p65 translocation and increased cytosolic IκBα levels.
  
  
  CONCLUSIONS
  15d-PGJ2 protects against endotoxin-induced acute lung injury, most likely through the reduction of proinflammatory protein levels during endotoxemia subsequent to the inhibition of NF-κB activation.
authors.affiliation: Department of Critical Care Medicine, General Hospital of Lanzhou Military Region, Lanzhou, Gansu 730050, China. Email: liutung@163.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, General Hospital of Lanzhou Military Region, Lanzhou, Gansu 730050, China.
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Geng
authors.affiliation: Department of Gastrointestinal Surgery, General Hospital of Lanzhou Military Region, Lanzhou, Gansu 730050, China.
authors.forename: Wankun
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, General Hospital of Lanzhou Military Region, Lanzhou, Gansu 730050, China.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, General Hospital of Lanzhou Military Region, Lanzhou, Gansu 730050, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, General Hospital of Lanzhou Military Region, Lanzhou, Gansu 730050, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D054360:Chemokine CXCL1 / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C477819:15-deoxyprostaglandin J2; D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D015230:Prostaglandin D2