Shimozawa Makoto, Naito Yuji, Manabe Hiroki, Uchiyama Kazuhiko, Kuroda Masaaki, Katada Kazuhiro, Yoshida Norimasa, Yoshikawa Toshikazu
Department of Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Redox Rep. 2004;9(6):370-5. doi: 10.1179/135100004225006902.
The aim of the present study was to assess the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), monocytic adhesion of human aortic endothelial cells (HAECs), and the production of intracellular reactive oxygen species (ROS), when HAECs were stimulated by 7-ketocholesterol. 7-ketocholesterol enhances surface expression of ICAM-1 and VCAM-1 as determined by EIA, induces their mRNA expression by RT-PCR, and stimulates adhesiveness of HAECs to U937 monocytic cells. We confirmed up-regulation of ROS production of HAECs treated with 7-ketocholesterol. Although the surface expression of ICAM-1 and VCAM-1 on HAECs treated with 7-ketocholesterol increased in a time-dependent manner, alpha-tocopherol inhibited this increase of the surface expression of ICAM-1 and VCAM-1. In the monocytic adhesion assay, adhesion of U937 to HAECs treated with 7-ketocholesterol was enhanced, but monoclonal anti-ICAM-1 and VCAM-1 antibodies reduced the endothelial adhesiveness. In conclusion, this study suggests that the endothelial adhesiveness to monocytic cells that was increased by 7-ketocholesterol was associated with enhanced expression of ICAM-1 and VCAM-1 mediated by ROS production.
本研究的目的是评估当人主动脉内皮细胞（HAECs）受到7-酮胆固醇刺激时，细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）的表达、HAECs的单核细胞黏附以及细胞内活性氧（ROS）的产生。通过酶免疫分析（EIA）测定，7-酮胆固醇可增强ICAM-1和VCAM-1的表面表达，通过逆转录聚合酶链反应（RT-PCR）诱导它们的mRNA表达，并刺激HAECs与U937单核细胞的黏附性。我们证实了用7-酮胆固醇处理的HAECs的ROS产生上调。尽管用7-酮胆固醇处理的HAECs上ICAM-1和VCAM-1的表面表达呈时间依赖性增加，但α-生育酚抑制了ICAM-1和VCAM-1表面表达的这种增加。在单核细胞黏附试验中，U937与用7-酮胆固醇处理的HAECs的黏附增强，但抗ICAM-1和VCAM-1单克隆抗体降低了内皮细胞的黏附性。总之，本研究表明，7-酮胆固醇增加的内皮细胞对单核细胞的黏附性与由ROS产生介导的ICAM-1和VCAM-1表达增强有关。
