In:
The Journal of Immunology, The American Association of Immunologists, Vol. 204, No. 1_Supplement ( 2020-05-01), p. 83.22-83.22
Abstract:
Dietary intake of ω3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid are beneficial for health control because ω3 fatty acids are metabolized to pro-resolution and anti-inflammatory lipid metabolites. We previously identified 17,18-epoxyeicosatetraenoic acid (17,18-EpETE) as a new lipid metabolite endogenously generated from EPA that exhibits potent anti-allergic and anti-inflammatory properties. However, the chemically synthesized 17,18-EpETE is enantiomeric mixture concerning to its epoxy group, i.e., 17(S),18(R)-EpETE and 17(R),18(S)-EpETE, and the stereostructural differences in anti-inflammatory effect of 17,18-EpETE has not been clarified. Because it is necessary to identify which isomer shows physiological function to develop it as a medicine, we evaluated stereospecific effects of 17(S),18(R)-EpETE and 17(R),18(S)-EpETE in amelioration of skin contact hypersensitivity. As a result, we found that anti-inflammatory activity was detected in 17(S),18(R)-EpETE, but not 17(R),18(S)-EpETE. In addition, we found that cytochrome P450 BM-3 derived from Bacillus megaterium stereoselectively converts EPA into 17(S),18(R)-EpETE, which effectively inhibited the development of contact hypersensitivity by inhibiting neutrophil migration in a G protein-coupled receptor 40-dependent manner. These results demonstrated that immune cells (e.g., neutrophils) distinguish biological active lipid metabolites stereoselectively for the control of their activity, which is a new strategy for the development of efficient immunotherapy.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.204.Supp.83.22
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2020
detail.hit.zdb_id:
1475085-5
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