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

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PPAR alpha
Lung Injury
Ligands
Bleomycin
Poly Adenosine Diphosphate Ribose
Interleukin-1beta
Knockout Mice
Tumor Necrosis Factor-alpha
indium-bleomycin
Thyroid Hormone Receptors
Retinoids
Cytoplasmic and Nuclear Receptors
Peroxidase
Transcription Factors
Immunohistochemistry
Steroids
Body Weight
Staining and Labeling

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Physiology

Cite this

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.

ROLE OF ENDOGENOUS AND EXOGENOUS LIGANDS FOR THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR alpha IN THE DEVELOPMENT OF BLEOMYCIN-INDUCED LUNG INJURY. / Genovese, Tiziana; Mazzon, Emanuela; Di Paola, Rosanna; Muià, Carmelo; Crisafulli, Concetta; Caputi, Achille P.; Cuzzocrea, Salvatore.

In: Shock, Vol. 24, No. 6, 12.2005, p. 547-555.

Research output: Contribution to journalArticle

Genovese, T, Mazzon, E, Di Paola, R, Muià, C, Crisafulli, C, Caputi, AP & 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, vol. 24, no. 6, pp. 547-555.
Genovese, Tiziana ; Mazzon, Emanuela ; Di Paola, Rosanna ; Muià, Carmelo ; Crisafulli, Concetta ; Caputi, Achille P. ; Cuzzocrea, Salvatore. / ROLE OF ENDOGENOUS AND EXOGENOUS LIGANDS FOR THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR alpha IN THE DEVELOPMENT OF BLEOMYCIN-INDUCED LUNG INJURY. In: Shock. 2005 ; Vol. 24, No. 6. pp. 547-555.
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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.",
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