Naito Yuji, Shimozawa Makoto, Kuroda Masaaki, Nakabe Nami, Manabe Hiroki, Katada Kazuhiro, Kokura Satoshi, Ichikawa Hiroshi, Yoshida Norimasa, Noguchi Noriko, Yoshikawa Toshikazu
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Atherosclerosis. 2005 May;180(1):19-25. doi: 10.1016/j.atherosclerosis.2004.11.017. Epub 2005 Jan 12.
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 alpha-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 alpha-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.
循环单核细胞迁移至内皮下间隙是通过内皮细胞上一些黏附分子的表达来实现的。在本研究中，我们使用人主动脉内皮细胞（HAECs），研究了一种氧甾醇的模型化合物25-羟基胆固醇是否能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对暴露于25-羟基胆固醇的HAECs的黏附。我们还旨在确定生育三烯酚对单核细胞与内皮细胞之间增强的相互作用的体外影响。我们发现，25-羟基胆固醇可通过ELISA增强表面表达，通过实时PCR诱导VCAM-1 mRNA表达，并以剂量依赖的方式刺激HAECs对U937单核细胞的黏附性。抗VCAM-1和抗CD11b单克隆抗体联合处理显著降低了单核细胞对25-羟基胆固醇刺激的HAECs的黏附。与α-生育酚相比，生育三烯酚对黏附分子表达和单核细胞黏附具有更显著的抑制作用。我们观察到，与α-生育酚以及α-、β-和γ-生育三烯酚相比，δ-生育三烯酚对单核细胞黏附具有最显著的抑制作用。生育三烯酚在HAECs中的积累水平比α-生育酚高约25至95倍。总之，这些结果表明，模型化合物25-羟基胆固醇可增强单核细胞与HAECs之间的相互作用，并且生育三烯酚相对于α-生育酚通过抑制VCAM-1表达对单核细胞黏附于HAECs具有显著的抑制作用。生育三烯酚的这些优异抑制作用可能取决于它们在细胞内的积累。
