| Omega-3 fatty acids cause dramatic changes in TLR4 and purinergic eicosanoid signaling. | |
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MedLine Citation:
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PMID: 22586114 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Dietary fish oil containing ω3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), elicit cardioprotective and anti-inflammatory effects through unresolved mechanisms that may involve competition and inhibition at multiple levels. Here, we report the effects of arachidonic acid (AA), EPA, and DHA supplementation on membrane incorporation, phospholipase A(2) catalyzed release, and eicosanoid production in RAW264.7 macrophages. Using a targeted lipidomics approach, we observed that Toll-like receptor 4 and purinergic receptor activation of supplemented cells leads to the release of 22-carbon fatty acids that potently inhibit cyclooxygenase pathways. This inhibition was able to shunt metabolism of AA to lipoxygenase pathways, augmenting leukotriene and other lipoxygenase mediator synthesis. In resident peritoneal macrophages, docosapentaenoic acid (DPA) was responsible for cyclooxygenase inhibition after EPA supplementation, offering fresh insights into how EPA exerts anti-inflammatory effects indirectly through elongation to 22-carbon DPA. |
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Authors:
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Paul C Norris; Edward A Dennis |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-05-14 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 109 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-05-30 Completed Date: 2012-08-24 Revised Date: 2013-02-19 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 8517-22 Citation Subset: IM |
Affiliation:
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Department of Chemistry/Biochemistry, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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pharmacology Animals Arachidonic Acid / metabolism, pharmacology Blotting, Western Cell Line Cell Membrane / drug effects, metabolism Cells, Cultured Docosahexaenoic Acids / metabolism, pharmacology Eicosanoids / metabolism Fatty Acids, Omega-3 / metabolism, pharmacology* Fatty Acids, Unsaturated / metabolism, pharmacology Gas Chromatography-Mass Spectrometry Lipopolysaccharides / pharmacology Lipoxygenase / metabolism Macrophages / cytology, drug effects*, metabolism Macrophages, Peritoneal / cytology, drug effects, metabolism Male Membrane Lipids / metabolism Mice Phospholipases A2 / metabolism Prostaglandin-Endoperoxide Synthases / metabolism Receptors, Purinergic P2X7 / metabolism Signal Transduction / drug effects* Toll-Like Receptor 4 / agonists, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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R01 GM64611/GM/NIGMS NIH HHS; T32 GM007752/GM/NIGMS NIH HHS; U54 GM069338/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Eicosanoids; 0/Fatty Acids, Omega-3; 0/Fatty Acids, Unsaturated; 0/Kdo2-lipid A; 0/Lipopolysaccharides; 0/Membrane Lipids; 0/Receptors, Purinergic P2X7; 0/Toll-Like Receptor 4; 25167-62-8/Docosahexaenoic Acids; 25448-00-4/docosapentaenoic acid; 506-32-1/Arachidonic Acid; 56-65-5/Adenosine Triphosphate; EC 1.13.11.12/Lipoxygenase; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases; EC 3.1.1.4/Phospholipases A2 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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