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 language | English |
|---|---|
| Pages (from-to) | 999-1010 |
| Number of pages | 12 |
| Journal | Journal of Leukocyte Biology |
| Volume | 79 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - May 2006 |
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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 journal › Article
}
TY - JOUR
T1 - The role of the peroxisome proliferator-activated receptor-α (PPAR-α) in the regulation of acute inflammation
AU - Cuzzocrea, Salvatore
AU - Mazzon, Emanuela
AU - Di Paola, Rosanna
AU - Peli, Angelo
AU - Bonato, Andrea
AU - Britti, Domenico
AU - Genovese, Tiziana
AU - Muià, Carmelo
AU - Crisafulli, Concetta
AU - Caputi, Achille P.
PY - 2006/5
Y1 - 2006/5
N2 - 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.
AB - 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.
KW - Carrageenan-induced paw edema
KW - Carrageenan-induced pleurisy
KW - Cytokines
KW - Neutrophil infiltration
UR - http://www.scopus.com/inward/record.url?scp=33745309774&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745309774&partnerID=8YFLogxK
U2 - 10.1189/jlb.0605341
DO - 10.1189/jlb.0605341
M3 - Article
C2 - 16501055
AN - SCOPUS:33745309774
VL - 79
SP - 999
EP - 1010
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 5
ER -