Document Detail


Omega-3 fatty acids cause dramatic changes in TLR4 and purinergic eicosanoid signaling.
MedLine Citation:
PMID:  22586114     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Paul C Norris; Edward A Dennis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-05-14
Journal Detail:
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:
Created Date:  2012-05-30     Completed Date:  2012-08-24     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8517-22     Citation Subset:  IM    
Affiliation:
Department of Chemistry/Biochemistry, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / 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:
R01 GM64611/GM/NIGMS NIH HHS; T32 GM007752/GM/NIGMS NIH HHS; U54 GM069338/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
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

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