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–κB. 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.
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7 March 2005
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March 07 2005
Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1
Makoto Arita,
Makoto Arita
1Center 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
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Francesca Bianchini,
Francesca Bianchini
1Center 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
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Julio Aliberti,
Julio Aliberti
2Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
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Alan Sher,
Alan Sher
2Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
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Nan Chiang,
Nan Chiang
1Center 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
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Song Hong,
Song Hong
1Center 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
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Rong Yang,
Rong Yang
3Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, CA 90089
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Nicos A. Petasis,
Nicos A. Petasis
3Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, CA 90089
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Charles N. Serhan
Charles N. Serhan
1Center 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
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Makoto Arita
1Center 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
Francesca Bianchini
1Center 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
Julio Aliberti
2Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Alan Sher
2Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
Nan Chiang
1Center 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
Song Hong
1Center 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
Rong Yang
3Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, CA 90089
Nicos A. Petasis
3Department of Chemistry and Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, CA 90089
Charles N. Serhan
1Center 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
CORRESPONDENCE Charles N. Serhan: [email protected]
Abbreviations used: ω-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.
Received:
September 30 2004
Accepted:
December 03 2004
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 201 (5): 713–722.
Article history
Received:
September 30 2004
Accepted:
December 03 2004
Citation
Makoto Arita, Francesca Bianchini, Julio Aliberti, Alan Sher, Nan Chiang, Song Hong, Rong Yang, Nicos A. Petasis, Charles N. Serhan; Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1 . J Exp Med 7 March 2005; 201 (5): 713–722. doi: https://doi.org/10.1084/jem.20042031
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