RT Journal Article
SR Electronic
T1 The Nuclear Receptor Peroxisome Proliferator-Activated Receptor-α Mediates the Anti-Inflammatory Actions of Palmitoylethanolamide
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 15
OP 19
DO 10.1124/mol.104.006353
VO 67
IS 1
A1 Jesse Lo Verme
A1 Jin Fu
A1 Giuseppe Astarita
A1 Giovanna La Rana
A1 Roberto Russo
A1 Antonio Calignano
A1 Daniele Piomelli
YR 2005
UL http://molpharm.aspetjournals.org/content/67/1/15.abstract
AB Palmitoylethanolamide (PEA), the naturally occurring amide of palmitic acid and ethanolamine, reduces pain and inflammation through an as-yet-uncharacterized mechanism. Here, we identify the nuclear receptor peroxisome proliferator-activated receptor-α (PPAR-α) as the molecular target responsible for the anti-inflammatory properties of PEA. PEA selectively activates PPAR-α in vitro with an EC50 value of 3.1 ± 0.4 μM and induces the expression of PPAR-α mRNA when applied topically to mouse skin. In two animal models, carrageenan-induced paw edema and phorbol ester-induced ear edema, PEA attenuates inflammation in wild-type mice but has no effect in mice deficient in PPAR-α. The natural PPAR-α agonist oleoylethanolamide (OEA) and the synthetic PPAR-α agonists GW7647 and Wy-14643 mimic these effects in a PPAR-α–dependent manner. These findings indicate that PPAR-α mediates the anti-inflammatory effects of PEA and suggest that this fatty-acid ethanolamide may serve, like its analog OEA, as an endogenous ligand of PPAR-α.