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The anti-inflammatory compound palmitoylethanolamide inhibits prostaglandin and hydroxyeicosatetraenoic acid production by a macrophage cell line
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
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2017 (English)In: Pharmacology Research & Perspectives, ISSN 2052-1707, Vol. 5, no 2, article id UNSP e00300Article in journal (Refereed) Published
Abstract [en]

The anti-inflammatory agent palmitoylethanolamide (PEA) reduces cyclooxygenase (COX) activity in vivo in a model of inflammatory pain. It is not known whether the compound reduces prostaglandin production in RAW264.7 cells, whether such an action is affected by compounds preventing the breakdown of endogenous PEA, whether other oxylipins are affected, or whether PEA produces direct effects upon the COX-2 enzyme. RAW264.7 cells were treated with lipopolysaccharide and interferon-c to induce COX-2. At the level of mRNA, COX-2 was induced > 1000-fold following 24 h of the treatment. Coincubation with PEA (10 mu mol/L) did not affect the levels of COX-2, but reduced the levels of prostaglandins D-2 and E-2 as well as 11- and 15-hydroxyeicosatetraenoic acid, which can also be synthesised by a COX-2 pathway in macrophages. These effects were retained when hydrolysis of PEA to palmitic acid was blocked. Linoleic acidderived oxylipin levels were not affected by PEA. No direct effects of PEA upon the oxygenation of either arachidonic acid or 2-arachidonoylglycerol by COX-2 were found. It is concluded that in lipopolysaccharide and interferon-c-stimulated RAW264.7 cells, PEA reduces the production of COX-2-derived oxylipins in a manner that is retained when its metabolism to palmitic acid is inhibited.

Place, publisher, year, edition, pages
JOHN WILEY & SONS LTD , 2017. Vol. 5, no 2, article id UNSP e00300
Keywords [en]
Palmitoylethanolamide, cyclooxygenase, prostaglandin, oxylipin, RAW264.7 cells, fatty acid amide drolase, N-acylethanolamine hydrolysing acid amidase, bootstrapped linear model
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:umu:diva-140988DOI: 10.1002/prp2.300ISI: 000407444900009PubMedID: 28357126OAI: oai:DiVA.org:umu-140988DiVA, id: diva2:1152469
Funder
Swedish Research Council, 12158Available from: 2017-10-25 Created: 2017-10-25 Last updated: 2018-06-09Bibliographically approved

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