The ethanolamide metabolite of DHA, docosahexaenoylethanolamine, shows immunomodulating effects in mouse peritoneal and RAW264.7 macrophages: evidence for a new link between fish oil and inflammation

• Published in: British journal of nutrition Vol. 105; no. 12; pp. 1798 - 1807
• Main Authors: Meijerink, Jocelijn, Plastina, Pierluigi, Vincken, Jean-Paul, Poland, Mieke, Attya, Mohamed, Balvers, Michiel, Gruppen, Harry, Gabriele, Bartolo, Witkamp, Renger F.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 28.06.2011; CABI Pub
• Subjects: adipose-tissue; Analysis of Variance; Animals; Biological and medical sciences; Cell Line; Chemokine CCL2 - metabolism; chemokines; Diet; Dietary supplements; dietary-fat; docosahexaenoic acid; Docosahexaenoic Acids - pharmacology; eicosapentaenoic acid; Enzyme-Linked Immunosorbent Assay; fatty-acid-composition; Feeding. Feeding behavior; Fish oils; Fish Oils - therapeutic use; food intake; Fundamental and applied biological sciences. Psychology; gene expression; Gene Expression - drug effects; Gene Expression - physiology; Immunology; Immunomodulation - drug effects; inflammation; Inflammation - metabolism; insulin-resistance; Lipopolysaccharides; macrophages; Macrophages - metabolism; Male; Metabolites; Mice; Mice, Inbred C57BL; monocyte chemoattractant protein-1; n-acylethanolamine; nitric oxide; nitric oxide synthase; Nitric Oxide Synthase - metabolism; Nutritional Immunology; omega-3 fatty acids; Peritoneal Cavity - cytology; polyunsaturated fatty acids; prasterone; reduces atherosclerosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Rodents; transcription (genetics); Vertebrates: anatomy and physiology, studies on body, several organs or systems; Inflammation; DHA; Macrophages; Docosahexaenoylethanolamine; Nitric oxide; Monocyte chemotactic protein-1; Monocyte; Metabolite; Rodentia; Fish oil; Protein; Vertebrata; Mammalia; Mouse; Animal; Macrophage
• ISSN: 0007-1145; 1475-2662
• DOI: 10.1017/S0007114510005635

Several mechanisms have been proposed for the positive health effects associated with dietary consumption of long-chain n-3 PUFA (n-3 LC-PUFA) including DHA (22 : 6n-3) and EPA (20 : 5n-3). After dietary intake, LC-PUFA are incorporated into membranes and can be converted to their corresponding N-acylethanolamines (NAE). However, little is known on the biological role of these metabolites. In the present study, we tested a series of unsaturated NAE on the lipopolysaccharide (LPS)-induced NO production in RAW264.7 macrophages. Among the compounds tested, docosahexaenoylethanolamine (DHEA), the ethanolamide of DHA, was found to be the most potent inhibitor, inducing a dose-dependent inhibition of NO release. Immune-modulating properties of DHEA were further studied in the same cell line, demonstrating that DHEA significantly suppressed the production of monocyte chemotactic protein-1 (MCP-1), a cytokine playing a pivotal role in chronic inflammation. In LPS-stimulated mouse peritoneal macrophages, DHEA also reduced MCP-1 and NO production. Furthermore, inhibition was also found to take place at a transcriptional level, as gene expression of MCP-1 and inducible NO synthase was inhibited by DHEA. To summarise, in the present study, we showed that DHEA, a DHA-derived NAE metabolite, modulates inflammation by reducing MCP-1 and NO production and expression. These results provide new leads in molecular mechanisms by which DHA can modulate inflammatory processes.