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

Seong Ho Yoo, Mohamed A. Abdelmegeed, Byoung Joon Song

Research output: Contribution to journalArticle

15 Scopus citations

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.

Original languageEnglish
Pages (from-to)366-371
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume436
Issue number3
DOIs
StatePublished - 5 Jul 2013

Keywords

  • Acute lung injury
  • Cytokines
  • Lipopolysaccharide
  • Nitroxidative stress
  • Peroxisome proliferator-activated receptor-α

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