| Summary: | 碩士 === 元培科技大學 === 生物技術研究所 === 102 === Eicosatrienoic acid (Δ11,14,17-20:3; ETrA), a unusual natural-ly-occurring n-3 polyunsaturated fatty acid (PUFA), is converted from the essential fatty acid α-linolenic acid (Δ9,12,15-18:3; ALA) by the action of elongase. Since n-3 PUFA has been reported to exert anti-inflammatory ef-fect, we speculated whether n-3 PUFA ETrA might also modulate immune responses. The objectives of this study were to synthesize and purify ETrA from alpha-linolenic acid (ALA) using combined techniques of chemical C2-elongation and column chromatography, and to determine whether ETrA modulated the n-6 PUFA composition in cellular phospholipids. Fur-thermore, the modulatory effect of ETrA and other n-3 PUFA on the pro-duction of pro-inflammatory mediators and signaling, such as nitric oxide (NO), prostaglandin E2 (PGE2), interlukin-6 (IL-6), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthetase (iNOS), cyclooxygenase-2 (COX-2) and nuclear factor factor-kappa B (NF-κB) of murine macro-phages in response to lipopolysaccharide (LPS) was examined. Results showed that there was no cytotoxicity when the ETrA concentration was less than 200 μM. ETrA was taken up, incorporated and metabolized by macrophages, and the proportions of cellular phospholipid ETrA and its metabolites increased in a dose-dependent manner. The incorporation of ETrA also decreased the proportions of linoleic acid (LA), dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA) as well, and reduced the proportion of total n-6 PUFA and monounsaturated fatty acids (MUFA). ETrA suppressed the production of NO and expression of iNOS in LPS-stimulated macrophages, respectively. However, no significant de-crease in the production of PGE2, IL-6 and TNF-α was observed. The mod-ulation of NO synthesis and iNOS expression was due, in part, to the inactivation of nuclear factor-kappa B (NF-κB). Results of the present study provided a better understanding of the function mechanisms and modula-tory effect of ETrA on inflammation, and useful information for the future development of medical uses and nutritional supplementation.
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