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

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 canbe 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 mostpotent inhibitor, inducing a dose-dependent inhibition of NO release. Immune-modulating properties of DHEA were further studied inthe same cell line, demonstrating that DHEA significantly suppressed the production of monocyte chemotactic protein-1 (MCP-1), a cytokineplaying a pivotal role in chronic inflammation. In LPS-stimulated mouse peritoneal macrophages, DHEA also reduced MCP-1 and NOproduction. Furthermore, inhibition was also found to take place at a transcriptional level, as gene expression of MCP-1 and inducible NOsynthase was inhibited by DHEA. To summarise, in the present study, we showed that DHEA, a DHA-derived NAE metabolite, modulatesinflammation by reducing MCP-1 and NO production and expression. These results provide new leads in molecular mechanisms by whichDHA can modulate inflammatory processes.