ROLE OF ENDOGENOUS AND EXOGENOUS LIGANDS FOR THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR alpha IN THE DEVELOPMENT OF BLEOMYCIN-INDUCED LUNG INJURY.

Tiziana Genovese, Emanuela Mazzon, Rosanna Di Paola, Carmelo Muià, Concetta Crisafulli, Achille P. Caputi, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

Abstract

The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a member of the nuclear receptor superfamily of ligand-dependent transcription factors related to retinoid, steroid, and thyroid hormone receptors. The aim of the present study was to examine the effects of endogenous and exogenous the PPAR-alpha ligand on the development of lung injury caused by bleomycin administration. Lung injury was induced in PPAR-alpha wild-type (WT) mice and PPAR-alpha knockout (KO) mice by intratracheal administration of bleomycin. An increase of immunoreactivity to poly-ADP-ribose, TNF-alpha, and IL-1 beta, as well as a significant loss of body weight and mortality was observed in the lung of bleomycin-treated PPAR-alpha WT mice. The absence of a functional PPAR-alpha gene in PPAR-alpha KO mice resulted in a significant augmentation of all the above-described parameters. On the contrary, the treatment of PPAR-alpha WT with WY-14643 (1 mg/kg daily) significantly reduced the degree of lung injury, the rise in myeloperoxidase activity, and the increase in staining (immunohistochemistry) for poly-ADP-ribose, TNF-alpha, and IL-1 beta caused by bleomycin administration. Thus, endogenous and exogenous PPAR-alpha ligands reduce the degree of lung injury induced by bleomycin in the mice. Therefore, we propose that the PPAR-alpha ligand may be useful in the treatment of lung injury.

Original languageEnglish
Pages (from-to)547-555
Number of pages9
JournalShock
Volume24
Issue number6
Publication statusPublished - Dec 2005

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

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    Genovese, T., Mazzon, E., Di Paola, R., Muià, C., Crisafulli, C., Caputi, A. P., & Cuzzocrea, S. (2005). ROLE OF ENDOGENOUS AND EXOGENOUS LIGANDS FOR THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR alpha IN THE DEVELOPMENT OF BLEOMYCIN-INDUCED LUNG INJURY. Shock, 24(6), 547-555.