Journal article
The fish oil ingredient, docosahexaenoic acid, activates cytosolic phospholipase A2 via GPR120 receptor to produce prostaglandin E2 and plays an anti‐inflammatory role in macrophages
Immunology, Vol.143(1), pp.81-95
09/2014
DOI: 10.1111/imm.12296
PMCID: PMC4137958
PMID: 24673159
Abstract
Summary
Docosahexaenoic acid (DHA) is one of the major ingredients of fish oil and has been reported to have anti‐inflammatory properties mediated through the GPR120 receptor. Whether cytosolic phospholipase A2 (cPLA2) and lipid mediators produced from cPLA2 activation are involved in the anti‐inflammatory role of DHA in macrophages has not been reported. We report here that DHA and the GPR120 agonist, GW9508, activate cPLA2 and cyclooxygenase 2 (COX‐2), and cause prostaglandin E2 (PGE2) release in a murine macrophage cell line RAW264.7 and in human primary monocyte‐derived macrophages. DHA and GW9508 activate cPLA2 via GPR120 receptor, G protein Gαq and scaffold protein β‐arrestin 2. Extracellular signal‐regulated kinase 1/2 activation is involved in DHA‐ and GW9508‐induced cPLA2 activation, but not p38 mitogen‐activated protein kinase. The anti‐inflammatory role of DHA and GW9508 is in part via activation of cPLA2, COX‐2 and production of PGE2 as a cPLA2 inhibitor or a COX‐2 inhibitor partially reverses the DHA‐ and GW9508‐induced inhibition of lipopolysaccharide‐induced interleukin‐6 secretion. The cPLA2 product arachidonic acid and PGE2 also play an anti‐inflammatory role. This effect of PGE2 is partially through inhibition of the nuclear factor‐κB signalling pathway and through the EP4 receptor of PGE2 because an EP4 inhibitor or knock‐down of EP4 partially reverses DHA inhibition of lipopolysaccharide‐induced interleukin‐6 secretion. Hence, DHA has an anti‐inflammatory effect partially through induction of PGE2.
Details
- Title: Subtitle
- The fish oil ingredient, docosahexaenoic acid, activates cytosolic phospholipase A2 via GPR120 receptor to produce prostaglandin E2 and plays an anti‐inflammatory role in macrophages
- Creators
- Yueqin Liu - National Institutes of HealthLi‐Yuan Chen - National Institutes of HealthMilena Sokolowska - National Institutes of HealthMichael Eberlein - University of IowaSara Alsaaty - National Institutes of HealthAsuncion Martinez‐Anton - National Institutes of HealthCarolea Logun - National Institutes of HealthHai‐Yan Qi - National Institutes of HealthJames H Shelhamer - National Institutes of Health
- Resource Type
- Journal article
- Publication Details
- Immunology, Vol.143(1), pp.81-95
- DOI
- 10.1111/imm.12296
- PMID
- 24673159
- PMCID
- PMC4137958
- ISSN
- 0019-2805
- eISSN
- 1365-2567
- Number of pages
- 15
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health
- Language
- English
- Date published
- 09/2014
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094730502771
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