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

Makoto Arita, Francesca Bianchini, Julio Aliberti, Alan Sher, Nan Chiang, Song Hong, Rong Yang, Nicos A. Petasis, Charles N. Serhan

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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-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.

Original languageEnglish
Pages (from-to)713-722
Number of pages10
JournalJournal of Experimental Medicine
Volume201
Issue number5
DOIs
Publication statusPublished - 2005 Mar 7
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Arita, M., Bianchini, F., Aliberti, J., Sher, A., Chiang, N., Hong, S., Yang, R., Petasis, N. A., & Serhan, C. N. (2005). Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1. Journal of Experimental Medicine, 201(5), 713-722. https://doi.org/10.1084/jem.20042031