title: Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury.
abstract: Acute lung injury (ALI) is a major cause of mortality and morbidity worldwide. The activation of peroxisome proliferator-activated receptor-α (PPARα) by its ligands, which include Wy-14643, has been implicated as a potential anti-inflammatory therapy. To address the beneficial efficacy of Wy-14643 for ALI along with systemic inflammation, the in vivo role of PPARα activation was investigated in a mouse model of lipopolysaccharide (LPS)-induced ALI. Using age-matched Ppara-null and wild-type mice, we demonstrate that the activation of PPARα by Wy-14643 attenuated LPS-mediated ALI. This was evidenced histologically by the significant alleviation of inflammatory manifestations and apoptosis observed in the lung tissues of wild-type mice, but not in the corresponding Ppara-null mice. This protective effect probably resulted from the inhibition of LPS-induced increases in pro-inflammatory cytokines and nitroxidative stress levels. These results suggest that the pharmacological activation of PPARα might have a therapeutic effect on LPS-induced ALI.
authors.affiliation: Seoul National University Hospital, Biomedical Research Institute and Institute of Forensic Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. yoosh@snu.ac.kr
authors.forename: Seong Ho
authors.initials: SH
authors.lastname: Yoo
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Abdelmegeed
authors.forename: Byoung-Joon
authors.initials: BJ
authors.lastname: Song
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000009:adverse effects; D008168:Lung / Q000187:drug effects / Q000473:pathology; D051379:Mice; D018384:Oxidative Stress; D047493:PPAR alpha / Q000819:agonists* / Q000378:metabolism; D011014:Pneumonia / Q000188:drug therapy / Q000473:pathology; D011743:Pyrimidines / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D047493:PPAR alpha; D011743:Pyrimidines; C577686:interleukin-6, mouse; D007371:Interferon-gamma; C006253:pirinixic acid
keywords: ALI; Acute lung injury; Cytokines; LPS; Lipopolysaccharide; MDA; Nitroxidative stress; PPARα; Peroxisome proliferator-activated receptor-α; STAT1; acute lung injury; lipopolysaccharide; malondialdehyde; peroxisome proliferator-activated receptor-α; signal transducer and activator of transcription 1