title: Resolvin D1 attenuates inflammation in lipopolysaccharide-induced acute lung injury through a process involving the PPARγ/NF-κB pathway.
abstract: BACKGROUND
  Docosahexaenoic acid (DHA) and DHA-derived lipid mediators have recently been shown to possess anti-inflammatory and pro-resolving properties. In fact, DHA can down-regulate lipolysaccharide (LPS)-induced activation of NF-κB via a PPARγ-dependent pathway. We sought to investigate the effects of the novel DHA-derived mediator resolvin D1 (RvD1) on LPS-induced acute lung injury and to determine whether these effects occur via a PPARγ-dependent pathway.
  
  
  METHODS
  BALB/c mice aged 6-8 weeks were randomly divided into seven groups: two control groups receiving saline or RvD1 (600 ng) without LPS; a control group receiving LPS only; an experimental group receiving RvD1 (300 ng) or RvD1 (600 ng), followed by LPS; a group receiving the PPARγ antagonist GW9662; and a group receiving GW9662, then RvD1 (600 ng) and finally LPS. LPS (50 μM) and saline were administered intratracheally. RvD1 was injected intravenously 24 h and 30 min before LPS, while GW9662 was injected intravenously 30 min before RvD1. Mice were killed at 6, 12, and 24 h. Samples of bronchoalveolar lavage fluid (BALF) were analyzed for cell counts and cytokine analysis. Lung tissues were collected for histology, Western blotting and electrophoretic mobility shift assays (EMSAs).
  
  
  RESULTS
  At all three time points, groups receiving either dose of RvD1 followed by LPS had significantly lower total leukocyte counts and levels of TNF-α and IL-6 levels in BALF than did the group given only LPS. RvD1 markedly attenuated LPS-induced lung inflammation at 24 h, based on hematoxylin-eosin staining of histology sections. RvD1 activated PPARγ and suppressed IκBα degradation and NF-κB p65 nuclear translocation, based on Western blots and EMSAs. The PPARγ inhibitor GW9662 partially reversed RvD1-induced suppression of IκBα degradation and p65 nuclear translocation.
  
  
  CONCLUSIONS
  These results suggest that RvD1 may attenuate lung inflammation of LPS-induced acute lung injury by suppressing NF-κB activation through a mechanism partly dependent on PPARγ activation.
authors.affiliation: Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Zenglin
authors.initials: Z
authors.lastname: Liao
authors.forename: Jiajia
authors.initials: J
authors.lastname: Dong
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Lingli
authors.initials: L
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Wen
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D047495:PPAR gamma; C518399:resolvin D1; D004281:Docosahexaenoic Acids