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.
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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)
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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
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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)
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