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Title: Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury

Abstract

Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for 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:
 [1];  [1]
  1. Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD (United States)
Publication Date:
OSTI Identifier:
22239649
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 436; Journal Issue: 3; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANIMAL TISSUES; APOPTOSIS; IN VIVO; INFLAMMATION; INHIBITION; INJURIES; LIGANDS; LIPIDS; LUNGS; LYMPHOKINES; MICE; MORTALITY; RECEPTORS; THERAPY; TRANSCRIPTION; TRANSDUCERS

Citation Formats

Yoo, Seong Ho, E-mail: yoosh@snu.ac.kr, Abdelmegeed, Mohamed A., and Song, Byoung-Joon. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury. United States: N. p., 2013. Web. doi:10.1016/J.BBRC.2013.05.073.
Yoo, Seong Ho, E-mail: yoosh@snu.ac.kr, Abdelmegeed, Mohamed A., & Song, Byoung-Joon. Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury. United States. https://doi.org/10.1016/J.BBRC.2013.05.073
Yoo, Seong Ho, E-mail: yoosh@snu.ac.kr, Abdelmegeed, Mohamed A., and Song, Byoung-Joon. 2013. "Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury". United States. https://doi.org/10.1016/J.BBRC.2013.05.073.
@article{osti_22239649,
title = {Activation of PPARα by Wy-14643 ameliorates systemic lipopolysaccharide-induced acute lung injury},
author = {Yoo, Seong Ho, E-mail: yoosh@snu.ac.kr and Abdelmegeed, Mohamed A. and Song, Byoung-Joon},
abstractNote = {Highlights: •Activation of PPARα attenuated LPS-mediated acute lung injury. •Pretreatment with Wy-14643 decreased the levels of IFN-γ and IL-6 in ALI. •Nitrosative stress and lipid peroxidation were downregulated by PPARα activation. •PPARα agonists may be potential therapeutic targets for 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.},
doi = {10.1016/J.BBRC.2013.05.073},
url = {https://www.osti.gov/biblio/22239649}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 436,
place = {United States},
year = {Fri Jul 05 00:00:00 EDT 2013},
month = {Fri Jul 05 00:00:00 EDT 2013}
}