College of Pharmacy, Chungnam National University, Yuseong-Ku, Teajon, Korea.
Br J Pharmacol. 2011 Mar;162(5):1119-35. doi: 10.1111/j.1476-5381.2010.01117.x.
Lysophosphatidylcholines (lysoPCs) with polyunsaturated acyl chains are known to exert anti-inflammatory actions. 15-Lipoxygeanation is crucial for anti-inflammatory action of polyunsaturated acylated lysoPCs. Here, the anti-inflammatory actions of 1-(15-hydroxyeicosapentaenoyl)-lysoPC (15-HEPE-lysoPC) and its derivatives were examined in a mechanistic analysis.
Anti-inflammatory actions of 15-HEPE-lysoPC in zymosan A-induced peritonitis of mice were examined by measuring plasma leakage and leucocyte infiltration, and determining levels of lipid mediators or cytokines.
When each lysoPC, administered i.v., was assessed for its ability to suppress zymosan A-induced plasma leakage, 15-HEPE-lysoPC was found to be more potent than 1-(15-hydroperoxyeicosapentaenoyl)-lysoPC or 1-eicosapentaenoyl-lysoPC. Separately, i.p. administration of 15-HEPE-lysoPC markedly inhibited plasma leakage, in contrast to 15-HEPE, which had only a small effect. 15-HEPE-lysoPC also decreased leucocyte infiltration. Moreover, it reduced the formation of LTC₄ and LTB₄, 5-lipoxygenation products, as well as the levels of pro-inflammatory cytokines. The time-course study indicated that 15-HEPE-lysoPC might participate in both the early inflammatory phase and resolution phase. Additionally, 15-HEPE-lysoPC administration caused a partial suppression of LTC₄-induced plasma leakage and LTB₄-induced leucocyte infiltration. In the metabolism study, peritoneal exudate was shown to contain lysoPC-hydrolysing activity, crucial for anti-inflammatory activity, and a system capable of generating lipoxin A from 15-hydroxy eicosanoid precursor.
15-HEPE-lysoPC, a precursor for 15-HEPE in target cells, induced anti-inflammatory actions by inhibiting the formation of pro-inflammatory leukotrienes and cytokines, and by enhancing the formation of lipoxin A. 15-HEPE-lysoPC might be one of many potent anti-inflammatory lipids in vivo.
具有多不饱和酰基链的溶血磷脂酰胆碱（lysoPC）已知具有抗炎作用。15-脂氧合酶是多不饱和酰化溶血磷脂酰胆碱抗炎作用的关键。在此，通过机制分析研究了 1-（15-羟基二十碳五烯酰基）-溶血磷脂酰胆碱（15-HEPE-溶血磷脂酰胆碱）及其衍生物的抗炎作用。
通过测量血浆渗漏和白细胞浸润，并测定脂质介质或细胞因子的水平，研究了 15-HEPE-溶血磷脂酰胆碱在酵母聚糖 A 诱导的小鼠腹膜炎中的抗炎作用。
当静脉内给予每种溶血磷脂酰胆碱以评估其抑制酵母聚糖 A 诱导的血浆渗漏的能力时，发现 15-HEPE-溶血磷脂酰胆碱比 1-（15-过氧二十碳五烯酰基）-溶血磷脂酰胆碱或 1-二十碳五烯酰基溶血磷脂酰胆碱更有效。另外，腹腔内给予 15-HEPE-溶血磷脂酰胆碱可显著抑制血浆渗漏，而 15-HEPE 仅具有较小的作用。15-HEPE-溶血磷脂酰胆碱还减少了白细胞浸润。此外，它减少了 LTC4 和 LTB4 的形成，5-脂氧合酶产物，以及促炎细胞因子的水平。时程研究表明，15-HEPE-溶血磷脂酰胆碱可能参与早期炎症阶段和消退阶段。此外，15-HEPE-溶血磷脂酰胆碱的给药导致 LTC4 诱导的血浆渗漏和 LTB4 诱导的白细胞浸润部分抑制。在代谢研究中，显示腹腔渗出液含有溶血磷脂酰胆碱水解活性，这对于抗炎活性至关重要，并且是一种能够从 15-羟基二十碳烷酸前体生成脂氧素 A 的系统。
15-HEPE-溶血磷脂酰胆碱是靶细胞中 15-HEPE 的前体，通过抑制促炎白三烯和细胞因子的形成并增强脂氧素 A 的形成来诱导抗炎作用。15-HEPE-溶血磷脂酰胆碱可能是体内许多有效的抗炎脂质之一。
