Identification and Structure Determination of Novel Anti-inflammatory Mediator Resolvin E3, 17,18-Dihydroxyeicosapentaenoic Acid

作者：Isobe Yosuke; Arita Makoto^*; Matsueda Shinnosuke; Iwamoto Ryo; Fujihara Takuji; Nakanishi Hiroki; Taguchi Ryo; Masuda Koji; Sasaki Kenji; Urabe Daisuke; Inoue Masayuki; Arai Hiroyuki

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287(13): 10525-10534.

DOI：10.1074/jbc.M112.340612

Bioactive mediators derived from omega-3 eicosapentaenoic acid (EPA) elicit potent anti-inflammatory actions. Here, we identified novel EPA metabolites, including 8,18-dihydroxyei-cosapentaenoic acid (8,18-diHEPE), 11,18-diHEPE, 12,18-diHEPE, and 17,18-diHEPE from 18-HEPE. Unlike resolvins E1 and E2, both of which are biosynthesized by neutrophils via the 5-lipoxygenase pathway, these metabolites are biosynthesized by eosinophils via the 12/15-lipoxygenase pathway. Among them, two stereoisomers of 17,18-diHEPE, collectively termed resolvin E3 (RvE3), displayed a potent anti-inflammatory action by limiting neutrophil infiltration in zymosan-induced peritonitis. The planar structure of RvE3 was unambiguously determined to be 17,18-dihydroxy-5Z, 8Z, 11Z, 13E, 15E-EPE by high resolution NMR, and the two stereoisomers were assigned to have 17,18R- and 17,18S-dihydroxy groups, respectively, using chemically synthesized 18R- and 18S-HEPE as precursors. Both 18R- and 18S-RvE3 inhibited neutrophil chemotaxis in vitro at low nanomolar concentrations. These findings suggest that RvE3 contributes to the beneficial actions of EPA in controlling inflammation and related diseases.

• 出版日期2012-3-23