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: Seong Ho Yoo, Mohamed A Abdelmegeed, Byoung-Joon Song
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 436 Issue 3 Pg. 366-71 (Jul 05 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 23727576 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Interleukin-6
• Lipopolysaccharides
• PPAR alpha
• Pyrimidines
• interleukin-6, mouse
• Interferon-gamma
• pirinixic acid

Topics

• Acute Lung Injury (chemically induced, drug therapy)
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Apoptosis
• Female
• Interferon-gamma (blood)
• Interleukin-6 (blood)
• Lipid Peroxidation
• Lipopolysaccharides (adverse effects)
• Lung (drug effects, pathology)
• Mice
• Oxidative Stress
• PPAR alpha (agonists, metabolism)
• Pneumonia (drug therapy, pathology)
• Pyrimidines (therapeutic use)