Tocotrienols reduce 25-hydroxycholesterol-induced monocyte-endothelial cell interaction by inhibiting the surface expression of adhesion molecules
Tocotrienols reduce 25-hydroxycholesterol-induced monocyte-endothelial cell interaction by inhibiting the surface expression of adhesion molecules
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DOI：
10.1016/j.atherosclerosis.2004.11.017
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发表时间：
2005-05-01
期刊：
影响因子：
5.3
通讯作者：
Noguchi, N
中科院分区：
文献类型：
--
作者：
Naito, Y;Shimozawa, M;Noguchi, N
循环中的单核细胞通过内皮细胞表面黏附分子的表达进入内皮下间隙。在本研究中，我们利用人主动脉内皮细胞(HAECs)，研究了氧化甾醇的模型化合物25-羟基胆固醇是否可以通过增加血管细胞黏附分子-1(VCAM-1)的表达来增强单核细胞与25-羟基胆固醇暴露的HAECs的黏附。我们还旨在确定生育三烯醇在体外对单核细胞和内皮细胞之间相互作用的增强作用。我们发现，25-羟基胆固醇增强了EL ISA法测定的细胞表面VCAM-1m RNA的表达，并以剂量依赖的方式刺激HAECs与U937单核细胞的黏附。联合应用抗VCAM-1和抗CD11b单抗可显著降低单核细胞对25-羟基胆固醇刺激的HAECs的粘附率。与α-生育酚相比，生育三烯醇对黏附分子表达和单核细胞黏附有更深的抑制作用。我们观察到，与α-生育酚、α-生育三烯醇、β-生育三烯醇和γ-生育三烯醇相比，β-生育三烯醇对单核细胞黏附的抑制作用最为明显。生育三烯醇在血管内皮细胞中的积聚水平大约是α-生育酚的25-95倍。这些结果表明，模型化合物25-羟基胆固醇可以增强单核细胞与HAECs的相互作用，生育三烯醇通过抑制VCAM-1的表达，相对于α-生育酚对单核细胞与HAECs的黏附有明显的抑制作用。生育三烯醇的这些优越的抑制作用可能依赖于它们在细胞内的积累。(C)2004爱思唯尔爱尔兰有限公司。保留所有权利。
The migration of circulating monocytes into the subendothelial space occurs through the expressing of some adhesion molecules on endothelial cells. In the present study, using human aortic endothelial cells (HAECs), we investigated whether a model compound for oxysterols, 25-hydroxycholesterol, can enhance the monocyte adherence to HAECs exposed to 25-hydroxycholesterol via increasing expression of vascular cell adhesion molecule-1 (VCAM-1). We also aimed to determine the in vitro effects of tocotrienols on the enhanced interaction between monocytes and endothelial cells. We found that 25-hydroxycholesterol enhances surface expression determined by ELISA, induces VCAM-1 mRNA expression by real time-PCR, and stimulates adhesiveness of HAECs to U937 monocytic cells in a dose-dependent fashion. The combination treatment with anti-VCAM-1 and anti-CD11b monoclonal antibodies significantly reduced the monocyte adherence to 25-hydroxycholesterol-stimulated HAECs. Compared to a-tocopherol, tocotrienols displayed a more profound inhibitory effect on adhesion molecule expression and monocytic cell adherence. We observed that delta-tocotrienol exerted a most profound inhibitory action on monocytic cell adherence when compared to a-tocopherol and alpha-, beta-, and gamma-tocotrienols. Tocotrienols accumulated in HAECs to levels approximately 25-95-fold greater than that of alpha-tocopherol. In conclusion, these results indicate that a model compound 25-hydroxycholesterol can enhance the interaction between monocytes and HAECs, and that tocotrienols had a profound inhibitory effect on monocytic cell adherence to HAECs relative to alpha-tocopherol via inhibiting the VCAM-1 expression. These superior inhibitory effects of tocotrienols may be dependent on their intracellular accumulation. (c) 2004 Elsevier Ireland Ltd. All rights reserved.