Source:http://linkedlifedata.com/resource/pubmed/id/17565008
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2007-8-21
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pubmed:abstractText |
Peroxisome proliferator-activated receptor (PPAR)-alpha is a nuclear transcription factor. Although the presence of this receptor in different areas of central nervous system (CNS) has been reported, its role remains unclear. Palmitoylethanolamide (PEA), a member of the fatty-acid ethanolamide family, acts peripherally as an endogenous PPAR-alpha ligand, exerting analgesic and anti-inflammatory effects. High levels of PEA in the CNS have been found, but the specific function of this lipid remains to be clarified. Using carrageenan-induced paw edema in mice, we show that i.c.v. administration of PEA may control peripheral inflammation through central PPAR-alpha activation. A single i.c.v. administration of 0.01 to 1 microg of PEA, 30 min before carrageenan injection, reduced edema formation in the mouse carrageenan test. This effect was mimicked by 0.01 to 1 microg of GW7647 [2-[[4-[2-[[(cyclohexylamino)carbonyl](4-cyclohexylbutyl)amino]ethyl]phenyl]thio]-2-methylpropanoic acid], a synthetic PPAR-alpha agonist. Moreover, central PEA administration significantly reduced the expression of the proinflammatory enzymes cyclooxygenase-2 and inducible nitric-oxide synthase, and it significantly restored carrageenan-induced PPAR-alpha reduction in the spinal cord. To investigate the mechanism by which i.c.v. PEA attenuated the development of carrageenan-induced paw edema, we evaluated inhibitor kappaB-alpha (I kappa B-alpha) degradation and nuclear factor-kappaB (NF-kappaB) p65 activation in the cytosolic or nuclear extracts from spinal cord tissue. PEA prevented IkB-alpha degradation and NF-kappaB nuclear translocation, confirming the involvement of this transcriptional factor in the control of peripheral inflammation. The obligatory role of PPAR-alpha in mediating the effects of PEA was confirmed by the lack of the compounds anti-inflammatory effects in mutant mice lacking PPAR-alpha. In conclusion, our data show for the first time that PPAR-alpha activation in the CNS can control peripheral inflammation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-3565
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pubmed:author |
pubmed-author:CalignanoAntonioA,
pubmed-author:CuzzocreaSalvatoreS,
pubmed-author:D'AgostinoGiuseppeG,
pubmed-author:EspositoEmanuelaE,
pubmed-author:IaconoAnnaA,
pubmed-author:La RanaGiovannaG,
pubmed-author:Lo VermeJesseJ,
pubmed-author:MeliRosariaR,
pubmed-author:PiomelliDanieleD,
pubmed-author:RasoGiuseppina MattaceGM,
pubmed-author:RussoRobertoR,
pubmed-author:SassoOscarO
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pubmed:issnType |
Print
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pubmed:volume |
322
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1137-43
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pubmed:meshHeading |
pubmed-meshheading:17565008-Animals,
pubmed-meshheading:17565008-Carrageenan,
pubmed-meshheading:17565008-Central Nervous System,
pubmed-meshheading:17565008-Drug Administration Routes,
pubmed-meshheading:17565008-Edema,
pubmed-meshheading:17565008-Inflammation,
pubmed-meshheading:17565008-Mice,
pubmed-meshheading:17565008-PPAR alpha,
pubmed-meshheading:17565008-Palmitic Acids
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pubmed:year |
2007
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pubmed:articleTitle |
Acute intracerebroventricular administration of palmitoylethanolamide, an endogenous peroxisome proliferator-activated receptor-alpha agonist, modulates carrageenan-induced paw edema in mice.
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pubmed:affiliation |
Department of Experimental Pharmacology, University of Naples Federico II, via D. Montesano 49, 80131 Naples, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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