Homocysteine stimulates the expression of monocyte chemoattractant protein-1 in endothelial cells leading to enhanced monocyte chemotaxis
Homocysteine stimulates the expression of monocyte chemoattractant protein-1 in endothelial cells leading to enhanced monocyte chemotaxis
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DOI：
10.1023/a:1017383916068
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发表时间：
2001-01-01
影响因子：
4.3
通讯作者：
O, K
中科院分区：
文献类型：
--
作者：
Sung, FL;Siow, YL;O, K
高同型半胱氨酸血症已被确定为动脉粥样硬化的独立危险因素。单核细胞浸润动脉壁是动脉粥样硬化形成过程中的关键事件之一。单核细胞趋化蛋白-1 (MCP-1) 是一种有效的趋化因子，可刺激单核细胞迁移至动脉壁内膜。高同型半胱氨酸血症患者动脉粥样硬化病变中单核细胞浸润增加的机制尚未阐明。本研究的目的是研究同型半胱氨酸对内皮细胞 MCP-1 产生的影响。将细胞与同型半胱氨酸一起孵育。在用病理浓度的同型半胱氨酸处理的细胞中，MCP-1蛋白的分泌显着增加（与对照相比增加195%）。这种效应伴随着内皮细胞中 MCP-1 mRNA 表达的增加（与对照相比增加 176%），从而导致单核细胞趋化性增强。 p38 MAP 激酶以及 p38 MAP 激酶途径的其他成员（包括 MKK3、MKK6、ATF-2 和 Elk-1）在同型半胱氨酸处理的细胞中被激活。同型半胱氨酸诱导的 MCP-1 表达和随后的单核细胞趋化性被 p38 MAP 激酶抑制剂 (SB203580) 阻断，表明 p38 MAP 激酶途径可能参与内皮细胞中同型半胱氨酸诱导的 MCP-1 表达。相比之下，星形孢菌素（一种蛋白激酶 C 抑制剂）对同型半胱氨酸诱导的 MCP-1 表达没有影响。总之，我们的结果表明同型半胱氨酸刺激内皮细胞中 MCP-1 的表达，从而增强单核细胞的趋化性。
Hyperhomocysteinemia has been identified as an independent risk factor for atherosclerosis. The infiltration of monocytes into the arterial wall is one of the key events during atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that stimulates the migration of monocytes into the intima of the arterial wall. The mechanism by which increased monocyte infiltration occurs in atherosclerotic lesions in patients with hyperhomocysteinemia has not been delineated. The objective of the present study was to investigate the effect of homocysteine on MCP-1 production in endothelial cells. Cells were incubated with homocysteine. The secretion of MCP-1 protein was significantly increased (195% as compared to the control) in cells treated with pathological concentrations of homocysteine. Such effect was accompanied by an increased expression of MCP-1 mRNA (176% as compared to the control) in endothelial cells which resulted in enhanced monocyte chemotaxis. The p38 MAP kinase as well as other members of the p38 MAP kinase pathway, including MKK3, MKK6, ATF-2 and Elk-1, were activated in homocysteine-treated cells. Homocysteine-induced MCP-1 expression and subsequent monocyte chemotaxis were blocked by a p38 MAP kinase inhibitor (SB203580) suggesting that the p38 MAP kinase pathway might be involved in homocysteine-induced MCP-1 expression in endothelial cells. In contrast, staurosporine, a protein kinase C inhibitor, had no effect on homocysteine-induced MCP-1 expression. In conclusion, our results indicate that homocysteine stimulates MCP-1 expression in endothelial cells leading to enhanced monocyte chemotaxis.