Food and Behaviour Research

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Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1.

Arita M, Bianchini F, Aliberti J, Sher A, Chiang N, Hong S, Yang R, Petasis NA, Serhan CN. (2005) J Exp Med. 201(5) 713-22 

Web URL: View PubMed abstract here

Abstract:

The essential fatty acid eicosapentaenoic acid (EPA) present in fish oils displays beneficial effects in a range of human disorders associated with inflammation including cardiovascular disease.

Resolvin E1 (RvE1), a new bioactive oxygenated product of EPA, was identified in human plasma and prepared by total organic synthesis. Results of bioaction and physical matching studies indicate that the complete structure of RvE1 is 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-EPA.

At nanomolar levels, RvE1 dramatically reduced dermal inflammation, peritonitis, dendritic cell (DC) migration, and interleukin (IL) 12 production. We screened receptors and identified one, denoted earlier as ChemR23, that mediates RvE1 signal to attenuate nuclear factor-kappaB. Specific binding of RvE1 to this receptor was confirmed using synthetic [(3)H]-labeled RvE1. Treatment of DCs with small interference RNA specific for ChemR23 sharply reduced RvE1 regulation of IL-12.

These results demonstrate novel counterregulatory responses in inflammation initiated via RvE1 receptor activation that provide the first evidence for EPA-derived potent endogenous agonists of antiinflammation.

FAB RESEARCH COMMENT:

Long-chain fatty acids of both the omega-3 and omega-6 series give rise to a wide range of 'lipid mediators' involved in cell signalling throughout the body and brain.

Resolvins are a special class of lipid mediators made from either omega-3 EPA (the E series resolvins) or omega-DHA (the D series resolvins). They play an active role in reolving inflammation, helping to explain the powerful anti-inflammatory effects of these omega-3 LC-PUFA (although EPA and DHA also have additional anti-inflammatory actions via other mechanisms).

This in vitro study involved isolating and characterising E-series resolvins from EPA, and confirming its anti-inflammatory actions.