期刊
INFLAMMATION
卷 34, 期 3, 页码 147-160出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-010-9218-z
关键词
anti-inflammatory; 2-docosahexaenoyl-lysoPC; zymosan A; nitric oxide LTC4; PGE(2); RAW 264.7 cell
资金
- Ministry of Education, Science and Technology [NRF 2009-0069242]
Lysophosphatidylcholines (lysoPCs) have been known to be bioactive lipid mediators, which take part in various biological and pathological processes. In the present study, we examined the anti-inflammatory actions of 2-docosahexaenoyl lysophosphatidylcholine (2-docosahexaenoyl-lysoPC) in vitro as well as in vivo systems. When RAW 264.7 cells were treated with 2-docoshexaenoyl-lysoPC, a concentration-dependent decrease of LPS-induced formation of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), or IL-6 was observed. Additionally, oral administration of 2-docosahexaenoyl-lysoPC was found to inhibit zymosan A-induced plasma leakage dose-dependently in mice with ED50 value of 50 mu g/kg and E (max) value of about 65%. Moreover, mechanistic study revealed that the anti-inflammatory action of 2-docosahexaenoyl-lysoPC seemed to be related largely to LTC4 inhibition, but not PGE(2) inhibition. Moreover, 2-(17-hydroperoxydocosahexaneoyl)-lysoPC, intravenously administrated, was more effective than 2-docosahexaenoyl-lysoPC in the inhibition of zymosan A-induced plasma leakage, suggesting that 2-(17-hydroperoxydocosahexaneoyl)-lysoPC, a product from oxygenation of 2-docosahexaenoyl-lysoPC by 15-lipoxygenase (LOX), may be an active metabolite, intimately responsible for anti-inflammatory actions, generated from 2-docosahexaenoyl-lysoPC. In a related study, 2-docosahexaenoyl-lysoPC was found to be more efficient than 1-docosahexaenoyl-lysoPC or docosahexaenoic acid (DHA) as substrate for 15-lipoxygenases such as soybean LOX-1, leukocyte 12/15-LOX, and human 15-LOX-2. Taken altogether, it is suggested that 2-docosahexaenoyl-lysoPC and its oxygenation products may exert anti-inflammatory action after oral administration.
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