Lysophosphatidylcholine containing docosahexaenoic acid at the sn-1 position is anti-inflammatory.
Lysophosphatidylcholine is known to be a lipid mediator in various cellular responses. In this study, we examined the anti-inflammatory actions of lysophosphatidylcholine containing docosahexaenoic acid esterified at the sn-1 position. First, in RAW 264.7 cells, DHA-lysoPtdCho suppressed the LPS-induced formation of NO concentration-dependently. However, ARA-lysoPtdCho showed a partial suppression, and LNA-lysoPtdCho had no significant effect. Additionally, DHA-lysoPtdCho also reduced the level of TNF-alpha or IL-6, but not PGE(2). In animal experiments, the i.v. administration of ARA-lysoPtdCho (150 or 500 mug/kg) prevented zymosan A-induced plasma leakage remarkably with a maximal efficacy (Emax) of 50%, in contrast to no effect with LNA-lysoPtdCho. Remarkably, DHA-lysoPtdCho suppressed zymosan A-induced plasma leakage with an ED(50) value of 46 mug/kg and an Emax value of around 95%. Additionally, mechanistic studies indicated that the anti-inflammatory action of DHA-lysoPtdCho was partially related to the reduced formation of LTC(4,) TNF-alpha, and IL-6. When the interval time between lysoPtdCho administration and zymosan A challenge was extended up to 2 h, such a suppressive action of DHA-lysoPtdCho was augmented, suggesting that a DHA-lysoPtdCho metabolite is important for anti-inflammatory action. In support of this, 17-HPDHA-lysoPtdCho showed a greater anti-inflammatory action than DHA-lysoPtdCho. Furthermore, a similar anti-inflammatory action was also observed with i.p. administration of DHA-lysoPtdCho or a 17(S)-hydroperoxy derivative. Additionally, oral administration of DHA-lysoPtdCho also expressed a significant anti-inflammatory action. Taken together, it is proposed that DHA-lysoPtdCho and its metabolites may be anti-inflammatory lipids in vivo systems.
Huang
Long Shuang
LS
College of Pharmacy, Chungnam National University, Gung-Dong 220, Yuseong-Gu, Taejon, 305-764, Korea.
Hung
Nguyen Dang
ND
Sok
Dai-Eun
DE
Kim
Mee Ree
MR
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D015232:Dinoprostone / Q000276:immunology; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000737:chemistry / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D015054:Zymosan / Q000276:immunology / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008244:Lysophosphatidylcholines; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D009569:Nitric Oxide; D015054:Zymosan; D015232:Dinoprostone