title: Docosahexaenoic acid attenuates in endocannabinoid synthesis in RAW 264.7 macrophages activated with benzo(a)pyrene and lipopolysaccharide.
abstract: Endocannabinoids are synthetized as a results of demand from membrane phospholipids. The formation and actions of these lipid mediators depend to a great extent on the prevalence of precursor fatty acid (FA), and can be influenced by diet or supplementation. The purpose of this study was to evaluate the interactive effects of lipopolysaccharide (LPS) and benzo(a)pyrene (BaP) in RAW 264.7 cells supplemented with docosahexaenoic acid (DHA). After LPS and/or BaP treatment in macrophages pre-incubated with DHA, a significant decrease in the amount of fatty acid was observed. The highest content of monounsaturated fatty acids was detected in RAW 264.7 cells co-treated with LPS and BaP. Significant interactions between LPS and BaP co-treatment in terms of endocannabinoid levels were observed in RAW 264.7 cells after DHA supplementation. The highest amount of endocannabinoids was detected in macrophages supplemented with DHA and co-treated with BaP and LPS: arachidonoyl ethanolamine AEA (5.9μg/mL), docosahexaenoyl ethanolamide DHEA (10.6μg/mL) and nervonoyl ethanolamide NEA (16.5μg/mL). The highest expression of cyclooxygenase (COX-2) and cannabinoid receptor 2 (CB2) was noted in macrophages supplemented with DHA and activated with LPS and BaP. Our data suggested a novel, CB2 receptor-dependent, environmental stress reaction in macrophages co-treated with LPS and BaP after supplementation with DHA. Despite the synergistic LPS and BaP action DHA potentiates the anti-inflammatory response in RAW 264.7 cells.
authors.affiliation: Department of Radioligands, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland. Electronic address: jargasinska@cm-uj.krakow.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Gdula-Argasińska
authors.affiliation: Chair of Toxicology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Bystrowska
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism; D016588:Anticarcinogenic Agents / Q000378:metabolism; D001095:Arachidonic Acids; D001564:Benzo(a)pyrene / Q000037:antagonists & inhibitors* / Q000633:toxicity; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D004357:Drug Synergism; D063388:Endocannabinoids / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D053284:Polyunsaturated Alkamides; D000067996:RAW 264.7 Cells; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000235:genetics / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D001095:Arachidonic Acids; D002273:Carcinogens; C571431:Cnr2 protein, mouse; D063388:Endocannabinoids; D005229:Fatty Acids, Monounsaturated; D008070:Lipopolysaccharides; C561061:N-docosahexaenoylethanolamide; D053284:Polyunsaturated Alkamides; D043885:Receptor, Cannabinoid, CB2; C000613946:nervonoyl ethanolamide; D004281:Docosahexaenoic Acids; D001564:Benzo(a)pyrene; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C078814:anandamide
keywords: Benzo(a)pyrene; Docosahexaenoyl ethanolamide; Endocannabinoids; Inflammation; Nervonoyl ethanolamide