title: 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.
abstract: 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.
authors.affiliation: Division of Human Nutrition, Wageningen University, PO Box 8129, 6700 EV, Wageningen, The Netherlands.
authors.forename: Jocelijn
authors.initials: J
authors.lastname: Meijerink
authors.affiliation: Division of Human Nutrition, Wageningen University, PO Box 8129, 6700 EV, Wageningen, The Netherlands.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Plastina
authors.affiliation: Laboratory of Food Chemistry, Wageningen University, PO Box 8129, 6700 EV, Wageningen, The Netherlands.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vincken
authors.affiliation: Division of Human Nutrition, Wageningen University, PO Box 8129, 6700 EV, Wageningen, The Netherlands.
authors.forename: Mieke
authors.initials: M
authors.lastname: Poland
authors.affiliation: Division of Human Nutrition, Wageningen University, PO Box 8129, 6700 EV, Wageningen, The Netherlands.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Attya
authors.affiliation: Division of Human Nutrition, Wageningen University, PO Box 8129, 6700 EV, Wageningen, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Balvers
authors.affiliation: Laboratory of Food Chemistry, Wageningen University, PO Box 8129, 6700 EV, Wageningen, The Netherlands.
authors.forename: Harry
authors.initials: H
authors.lastname: Gruppen
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università della Calabria, 87036, Arcavacata di Rende, Cosenza, Italy.
authors.forename: Bartolo
authors.initials: B
authors.lastname: Gabriele
authors.affiliation: Division of Human Nutrition, Wageningen University, PO Box 8129, 6700 EV, Wageningen, The Netherlands.
authors.forename: Renger F
authors.initials: RF
authors.lastname: Witkamp
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005395:Fish Oils / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D056747:Immunomodulation / Q000187:drug effects*; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018932:Chemokine CCL2; D005395:Fish Oils; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D019001:Nitric Oxide Synthase