Huang Long Shuang, Hung Nguyen Dang, Sok Dai-Eun, Kim Mee Ree
College of Pharmacy, Chungnam National University, Gung-Dong 220, Yuseong-Gu, Taejon, 305-764, Korea.
Lipids. 2010 Mar;45(3):225-36. doi: 10.1007/s11745-010-3392-5. Epub 2010 Feb 18.
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.
溶血磷脂酰胆碱是已知的参与多种细胞反应的脂质介质。在本研究中，我们检测了在sn-1位含有二十二碳六烯酸酯化的溶血磷脂酰胆碱的抗炎作用。首先，在RAW 264.7细胞中，DHA-溶血磷脂酰胆碱浓度依赖性地抑制LPS诱导的NO生成。然而，ARA-溶血磷脂酰胆碱表现出部分抑制作用，而LNA-溶血磷脂酰胆碱无显著作用。此外，DHA-溶血磷脂酰胆碱还降低了TNF-α或IL-6的水平，但对PGE(2)无影响。在动物实验中，静脉注射ARA-溶血磷脂酰胆碱（150或500μg/kg）可显著预防酵母聚糖A诱导的血浆渗漏，最大效应（Emax）为50%，相比之下，LNA-溶血磷脂酰胆碱无此作用。值得注意的是，DHA-溶血磷脂酰胆碱以46μg/kg的ED(50)值和约95%的Emax值抑制酵母聚糖A诱导的血浆渗漏。此外，机制研究表明，DHA-溶血磷脂酰胆碱的抗炎作用部分与LTC(4)、TNF-α和IL-6生成减少有关。当溶血磷脂酰胆碱给药与酵母聚糖A攻击之间的间隔时间延长至2小时时，DHA-溶血磷脂酰胆碱的这种抑制作用增强，表明DHA-溶血磷脂酰胆碱的一种代谢产物对其抗炎作用很重要。支持这一观点的是，17-HPDHA-溶血磷脂酰胆碱比DHA-溶血磷脂酰胆碱表现出更强的抗炎作用。此外，腹腔注射DHA-溶血磷脂酰胆碱或其17(S)-氢过氧化物衍生物也观察到类似的抗炎作用。此外，口服DHA-溶血磷脂酰胆碱也表现出显著的抗炎作用。综上所述，推测DHA-溶血磷脂酰胆碱及其代谢产物可能是体内系统中的抗炎脂质。
