The role of the peroxisome proliferator-activated receptor-α (PPAR-α) in the regulation of acute inflammation

Salvatore Cuzzocrea, Emanuela Mazzon, Rosanna Di Paola, Angelo Peli, Andrea Bonato, Domenico Britti, Tiziana Genovese, Carmelo Muià, Concetta Crisafulli, Achille P. Caputi

Research output: Contribution to journalArticle

Abstract

The peroxisome proliferator-activated receptor-α (PPAR-α) 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 evaluate the role of the PPAR-α receptor on the development of acute inflammation. To address this question, we used two animal models of acute inflammation (carrageenan-induced paw edema and carrageenan-induced pleurisy). We report here that when compared with PPAR-α wild-type mice, PPAR-α knockout mice (PPAR-αKO) mice experienced a higher rate of the extent and severity when subjected to carrageenan injection in the paw edema model or to carrageenan administration in the pleurisy model. In particular, the absence of a functional PPAR-α gene in PPAR-αKO mice resulted in a significant augmentation of various inflammatory parameters (e.g., enhancement of paw edema, pleural exudate formation, mononuclear cell infiltration, and histological injury) in vivo. Furthermore, the absence of a functional PPAR-α gene enhanced the staining (immunohistochemistry) for FAS ligand in the paw and in the lung and the expression of tumor necrosis factor α and interleukin-1β in the lungs of carrageenan-treated mice. In conclusion, the increased inflammatory response observed in PPAR-αKO mice strongly suggests that a PPAR-α pathway modulates the degree of acute inflammation in the mice.

Original languageEnglish
Pages (from-to)999-1010
Number of pages12
JournalJournal of Leukocyte Biology
Volume79
Issue number5
DOIs
Publication statusPublished - May 2006

Keywords

  • Carrageenan-induced paw edema
  • Carrageenan-induced pleurisy
  • Cytokines
  • Neutrophil infiltration

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Cuzzocrea, S., Mazzon, E., Di Paola, R., Peli, A., Bonato, A., Britti, D., Genovese, T., Muià, C., Crisafulli, C., & Caputi, A. P. (2006). The role of the peroxisome proliferator-activated receptor-α (PPAR-α) in the regulation of acute inflammation. Journal of Leukocyte Biology, 79(5), 999-1010. https://doi.org/10.1189/jlb.0605341