ArticleImmunology2014
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.
Article in Immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 112 citations in OpenAlex.
- Docosahexaenoic diet supplementation, exercise and temperature affect cytokine production by lipopolysaccharide-stimulated mononuclear cells.Journal of physiology and biochemistry · 2016Trial
- Effects of dietary Docosahexaenoic, training and acute exercise on lipid mediators.Journal of the International Society of Sports Nutrition · 2016Trial
- The roles of free-fatty acid receptors in the pathophysiology of renal disorders.The Journal of pharmacology and experimental therapeutics · 2026Review
- Late gestational exposure to flutamide alters stromal composition and immune landscape in the rat mammary gland during pre-puberty, peri-puberty, and adulthood.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Effects of intravenous lipid emulsions on Jurkat cells assessed using label-free deformability cytometry.Scientific reports · 2025Article
- Molecular Mechanisms and Clinical Implications of Complex Prehabilitation in Colorectal Cancer Surgery: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Effects of Docosahexaenoic Acid on Prostate Cancer.Journal of xenobiotics · 2025Review
- Immunomodulatory Effects of Omega-3 Fatty Acids: Mechanistic Insights and Health Implications.Molecular nutrition & food research · 2025Review
- Biased agonism at free-fatty acid receptor-4 (FFA4/GPR120).Pharmacology & therapeutics · 2025Review
- Orbital Fat is an Observation Model to Provide Insights into Adipocyte Hypertrophy and Hyperplasia During White Adipose Tissue Expansion.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Review
- Causal Relationships between Polyunsaturated Fatty Acids and Colon Polyps: A Two-Sample Mendelian Randomization Study.Nutrients · 2024Article
- Metabolite-sensing GPCRs controlling interactions between adipose tissue and inflammation.Frontiers in endocrinology · 2023Review
- Signaling through Free Fatty Acid Receptor 4 Attenuates Cardiometabolic Disease.Physiology (Bethesda, Md.) · 2022Review
- Free fatty acid receptor 4 responds to endogenous fatty acids to protect the heart from pressure overload.Cardiovascular research · 2022Article
- Macrophage-Mediated Immune Responses: From Fatty Acids to Oxylipins.Molecules (Basel, Switzerland) · 2021Review
- Anti-inflammatory effects and enhancing immune response of freshwater hybrid catfish oil in RAW264.7 cells.Experimental and therapeutic medicine · 2021Article
- Review
- GPR120/FFAR4 Pharmacology: Focus on Agonists in Type 2 Diabetes Mellitus Drug Discovery.Journal of medicinal chemistry · 2021Article
- Can N-3 polyunsaturated fatty acids be considered a potential adjuvant therapy for COVID-19-associated cardiovascular complications?Pharmacology & therapeutics · 2021Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.