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

73 Citations (Scopus)

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

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Peroxisome Proliferator-Activated Receptors
Inflammation
Carrageenan
Edema
Pleurisy
Ligands
Thyroid Hormone Receptors
Lung
Retinoids
Exudates and Transudates
Cytoplasmic and Nuclear Receptors
Interleukin-1
Knockout Mice
Genes
Transcription Factors
Animal Models
Tumor Necrosis Factor-alpha
Immunohistochemistry
Steroids
Staining and Labeling

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

The role of the peroxisome proliferator-activated receptor-α (PPAR-α) in the regulation of acute inflammation. / Cuzzocrea, Salvatore; Mazzon, Emanuela; Di Paola, Rosanna; Peli, Angelo; Bonato, Andrea; Britti, Domenico; Genovese, Tiziana; Muià, Carmelo; Crisafulli, Concetta; Caputi, Achille P.

In: Journal of Leukocyte Biology, Vol. 79, No. 5, 05.2006, p. 999-1010.

Research output: Contribution to journalArticle

Cuzzocrea, S, Mazzon, E, Di Paola, R, Peli, A, Bonato, A, Britti, D, Genovese, T, Muià, C, Crisafulli, C & Caputi, AP 2006, 'The role of the peroxisome proliferator-activated receptor-α (PPAR-α) in the regulation of acute inflammation', Journal of Leukocyte Biology, vol. 79, no. 5, pp. 999-1010. https://doi.org/10.1189/jlb.0605341
Cuzzocrea, Salvatore ; Mazzon, Emanuela ; Di Paola, Rosanna ; Peli, Angelo ; Bonato, Andrea ; Britti, Domenico ; Genovese, Tiziana ; Muià, Carmelo ; Crisafulli, Concetta ; Caputi, Achille P. / The role of the peroxisome proliferator-activated receptor-α (PPAR-α) in the regulation of acute inflammation. In: Journal of Leukocyte Biology. 2006 ; Vol. 79, No. 5. pp. 999-1010.
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