Identification of 14,20-dihydroxy-docosahexaenoic acid as a novel anti-inflammatory metabolite

Docosahexaenoic acid (DHA) exhibits anti-inflammatory activity related to some of its oxygenated metabolites, such as D-series resolvins, protectin and maresin. Here, we analysed the lipids in inflammatory exudates using liquid chromatography–tandem mass spectrometry and identified a novel DHA metabolite, 14,20-dihydroxy-DHA (14,20-diHDHA) and showed that it is biosynthesized by eosinophils through the 12/15-lipoxygenase pathway. The chemical structure of the dominant 14,20-diHDHA isomer, which is endogenously biosynthesized by eosinophils, was identified as 14S,20R-diHDHA using chemically synthesized stereoisomers. Nanogram doses of 14,20-diHDHA displayed a potent anti-inflammatory action by limiting neutrophil infiltration in zymosan-induced peritonitis. The in vivo formation and potent anti-inflammatory action of 14,20-diHDHA may contribute to the protective effects of DHA.

Source: Journal of Biochemistry - November 26, 2014 Category: Biochemistry Authors: Yokokura, Y., Isobe, Y., Matsueda, S., Iwamoto, R., Goto, T., Yoshioka, T., Urabe, D., Inoue, M., Arai, H., Arita, M. Tags: Regular Papers Source Type: research