GW0742, a high affinity PPAR-β/δ agonist reduces lung inflammation induced by bleomycin instillation in mice.

M. Galuppo, R. Di Paola, E. Mazzon, E. Esposito, I. Paterniti, A. Kapoor, C. Thiemermann, S. Cuzzocrea

Research output: Contribution to journalArticle

Abstract

Peroxisome Proliferator-Activated Receptor β/δ belongs to a family of ligand-activated transcription factors. Recent data have clarified its metabolic roles and enhanced the potential role of this receptor as a pharmacological target. Moreover, although its role in acute inflammation remains unclear, being the nuclear receptor PPAR β/δ widely expressed in many tissues, including the vascular endothelium, we assume that the infiltration of PMNs into tissues, a prominent feature in inflammation, may also be related to PPAR β/δ. Mice subjected to intratracheal instillation of bleomycin (BLEO, 1 mg/kg), a glycopeptide produced by the bacterium Streptomyces verticillus, develop lung inflammation and injury characterized by a significant neutrophil infiltration and tissue oedema. Therefore, the aim of this study is to investigate the effects of GW0742, a synthetic high affinity PPAR β/δ agonist, and its possible role in preventing the advance of inflammatory and apoptotic processes induced by bleomycin, that long-term leads to the appearance of pulmonary fibrosis. Our data showed that GW0742-treatment (0.3 mg/Kg, 10 percent DMSO, i.p.) has therapeutic effects on pulmonary damage, decreasing many inflammatory and apoptotic parameters detected by measurement of: 1) cytokine production; 2) leukocyte accumulation, indirectly measured as decrease of myeloperoxidase (MPO) activity; 3) IkBα degradation and NF-kB nuclear translocation; 4) ERK phosphorylation; 5) stress oxidative by NO formation due to iNOS expression; 6) nitrotyrosine and PAR localization; 7) the degree of apoptosis, evaluated by Bax and Bcl-2 balance, FAS ligand expression and TUNEL staining. Taken together, our results clearly show that GW0742 reduces the lung injury and inflammation due to the intratracheal BLEO--instillation in mice.

Original languageEnglish
Pages (from-to)1033-1046
Number of pages14
JournalInternational Journal of Immunopathology and Pharmacology
Volume23
Issue number4
Publication statusPublished - Oct 2010

Fingerprint

Peroxisome Proliferator-Activated Receptors
Pneumonia
Bleomycin
Lung Injury
Ligands
Inflammation
Neutrophil Infiltration
Glycopeptides
NF-kappa B
Pulmonary Fibrosis
Vascular Endothelium
In Situ Nick-End Labeling
Streptomyces
Therapeutic Uses
Cytoplasmic and Nuclear Receptors
Dimethyl Sulfoxide
Peroxidase
Edema
Oxidative Stress
Leukocytes

ASJC Scopus subject areas

  • Pharmacology
  • Immunology
  • Immunology and Allergy

Cite this

GW0742, a high affinity PPAR-β/δ agonist reduces lung inflammation induced by bleomycin instillation in mice. / Galuppo, M.; Di Paola, R.; Mazzon, E.; Esposito, E.; Paterniti, I.; Kapoor, A.; Thiemermann, C.; Cuzzocrea, S.

In: International Journal of Immunopathology and Pharmacology, Vol. 23, No. 4, 10.2010, p. 1033-1046.

Research output: Contribution to journalArticle

Galuppo, M, Di Paola, R, Mazzon, E, Esposito, E, Paterniti, I, Kapoor, A, Thiemermann, C & Cuzzocrea, S 2010, 'GW0742, a high affinity PPAR-β/δ agonist reduces lung inflammation induced by bleomycin instillation in mice.', International Journal of Immunopathology and Pharmacology, vol. 23, no. 4, pp. 1033-1046.
Galuppo, M. ; Di Paola, R. ; Mazzon, E. ; Esposito, E. ; Paterniti, I. ; Kapoor, A. ; Thiemermann, C. ; Cuzzocrea, S. / GW0742, a high affinity PPAR-β/δ agonist reduces lung inflammation induced by bleomycin instillation in mice. In: International Journal of Immunopathology and Pharmacology. 2010 ; Vol. 23, No. 4. pp. 1033-1046.
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