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¹ Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115
² Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
³ Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, CA 90089

CORRESPONDENCE Charles N. Serhan: cnserhan{at}zeus.bwh.harvard.edu

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–B. Specific binding of RvE1 to this receptor was confirmed using synthetic [³H]-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.

Abbreviations used: -3 PUFA, omega-3 polyunsaturated fatty acid; COX, cyclooxygenase; EAR, extracellular acidification rate; EPA, eicosapentaenoic acid; ERK, extracellular signal-regulated kinase; GPCR, G-protein–coupled receptor; HEPE, hydroxyeicosapentaenoic acid; LC-MS/MS, liquid chromatography tandem mass spectrometry; LO, lipoxygenase; LXA₄, lipoxin A₄; MAP, mitogen-activated protein; PTX, pertussis toxin; RvE1, resolvin E1; siRNA, small interference RNA; STAg, soluble tachyzoite antigen.

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