ADMA induces monocyte adhesion via activation of chemokine receptors in cultured THP-1 cells
ADMA induces monocyte adhesion via activation of chemokine receptors in cultured THP-1 cells
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DOI：
10.1016/j.cyto.2008.05.001
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发表时间：
2008-08-01
期刊：
影响因子：
3.8
通讯作者：
Xie, Xiumei
中科院分区：
文献类型：
--
作者：
Chen, Meifang;Li, Yuanjian;Xie, Xiumei
不对称二甲基精氨酸(ADMA)是一种内源性一氧化氮合酶抑制物，也是动脉粥样硬化(AS)发生发展的重要炎症因子。本研究旨在探讨ADMA对血管紧张素II诱导的单核细胞黏附的影响。人单核细胞(THP-1)或分离的外周血单核细胞(PBMC)与血管紧张素转换酶(Ang IF)(10-6M)或外源性ADMA(30mU M)孵育4或24 h，不加氯沙坦或抗氧化剂PDTC。在培养的THP-1细胞中，Ang II(10(-6)M)作用24 h，可增加培养液中ADMA水平，上调精氨酸甲基转移酶(PRMT)蛋白的表达，降低二甲基精氨酸二甲氨基水解酶(DDAH)的活性。Ang II和ADMA均可增加单核细胞与人脐静脉内皮细胞(HUVECs)的黏附，上调单核细胞趋化蛋白(MCP)-1、白介素8(IL)-8和肿瘤坏死因子(TNF)-α水平，上调CCR2和CXCR2的表达，同时增加ROS的生成和核因子-kappaB的激活。在分离的健康人PBMC中，ADMA可上调CXCR2mRNA的表达，该作用可被氯沙坦(10 MU M)减弱，而ADMA对CCR2的表面蛋白表达无影响。提示ADMA可能通过ROS/NF-kappa B途径激活趋化因子受体，参与Ang II诱导的单核细胞黏附。(C)2008爱思唯尔有限公司。保留所有权利。
Asymmetric dimethylarginine (ADMA), an endogenous NOS inhibitor, is also an important inflammatory factor contributing to the development of atherosclerosis (AS). The present study was to test the effect of ADMA on angiotensin (Ang) II-induced monocytic adhesion. Human monocytoid cells (THP-1) or isolated peripheral blood monocyte cells (PBMCs) were incubated with Ang If (10(-6) M) or exogenous ADMA (30 mu M) for 4 or 24 h in the absence or presence of losartan or antioxidant PDTC. In cultured THP-1 cells, Ang II (10(-6) M) for 24 h elevated the level of ADMA in the medium, upregulated the protein expression of protein arginine methyltransferase (PRMT) and decreased the activity of dimethylarginine dimethylaminohydrolase (DDAH). Both of Ang II and ADMA increased monocytic adhesion to human umbilical vein endothelial cells (HUVECs), elevated the levels of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha and upregulated CCR2 and CXCR2 mRNA expression, concomitantly with increase in reactive oxygen species (ROS) generation and activation of nuclear factor (NF)-kappa B. Pretreatment with losartan (10 mu M) or PDTC (10 mu M) abolished the effects mediated by Ang II or ADMA. In isolated PBMCs from healthy individuals, ADMA upregulated the expression of CXCR2 mRNA, which was attenuated by losartan (10 mu M), however, ADMA had no effect on surface protein expression of CCR2. The present results suggest that ADMA may be involved in monocytic adhesion induced by Ang II via activation of chemokine receptors by ROS/NF-kappa B pathway. (c) 2008 Elsevier Ltd. All rights reserved.