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.

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

PLASTINA, Pierluigi;GABRIELE, Bartolo;
2011-01-01

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 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.
2011
DHA; Inflammation; Macrophages
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11770/136080
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