Macrophage inflammatory protein-1β induced cell adhesion with increased intracellular reactive oxygen species
Macrophage inflammatory protein-1β induced cell adhesion with increased intracellular reactive oxygen species
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DOI：
10.1016/j.yjmcc.2009.03.012
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发表时间：
2009-07-01
影响因子：
5
通讯作者：
Rakugi, Hiromi
中科院分区：
文献类型：
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作者：
Tatara, Yuji;Ohishi, Mitsuru;Rakugi, Hiromi
为了研究巨噬细胞炎性蛋白-1 β（MIP-1 β）在动脉粥样硬化发生发展中的作用，我们设计了一项体外研究来阐明单核细胞-内皮细胞粘附通过细胞内活性氧（ROS）的机制。血管紧张素II（Ang II）用作阳性对照。此外，我们研究了MIP-1 β作为高血压患者卒中和心血管事件预测因子的有效性。MIP-1 β或AngII刺激显著增加ROS产生和THP-1细胞与发炎的人脐静脉内皮细胞的粘附。在刺激的THP-1细胞中，通过以下方式抑制细胞粘附和ROS产生：用N-乙酰半胱氨酸、二亚苯基碘鎓或PEG-过氧化氢酶抑制ROS信号传导;用siRNA或LY 294002抑制PI 3 K γ;以及通过Rac 1 siRNA。MIP-1 β或AngII刺激不增加整合素、极晚期抗原4（VLA-4）和淋巴细胞功能相关抗原1（LFA-1）的表面表达，但使用抗VLA-4或抗LFA-1抗体可降低细胞粘附。此外，MIP-1 β或AngII刺激的细胞粘附和ROS产生被氟伐他汀完全抑制。在我们的临床研究中，通过考克斯比例风险模型，MIP-1 β最高四分位数的患者显示卒中和心血管事件的风险较高。总之，MIP-1 β通过PI 3 k-Rac 1级联反应通过氧化应激直接诱导细胞粘附至内皮细胞。血清MIP-1 β水平可能是一个有用的预测动脉粥样硬化-心血管事件在高血压patients. Condensedabstract：我们设计了一个体外调查，以检查MIP-1 β的作用动脉粥样硬化的发展，包括细胞粘附涉及CAMS和ROS的生产，相比血管紧张素II。此外，我们在一项小型队列研究中调查了MIP-1 β对高血压患者卒中和心血管事件的预后影响。(C)2009爱思唯尔公司All rights reserved.
To investigate the role of macrophage inflammatory protein-1 beta (MIP-1 beta) in the development of atherosclerosis, we designed an in vitro study to elucidate the mechanisms of monocyte-endothelium adhesion via intracellular reactive oxygen species (ROS). Angiotensin II (Ang II) was used as a positive control. Furthermore, we examined the efficacy of MIP-1 beta as a predictor of stroke and cardiovascular events in hypertensive patients. MIP-1 beta or AngII stimulation significantly increased ROS production and adhesion of THP-1 cells to inflamed human umbilical vein endothelial cells. Cell adhesion and ROS production were inhibited in stimulated THP-1 cells by: inhibition of ROS signaling with N-acetylcysteine, diphenyleneiodonium, or PEG-Catalase; inhibition of PI3K gamma with siRNA or LY294002; and by Rac1 siRNA. The MIP-1 beta or AngII stimulation did not increase surface expression of integrins, very late antigen 4 (VLA-4) and lymphocyte function-associated antigen 1 (LFA-1), but cell adhesion was reduced by using an antiVLA-4 or an antiLFA-1 antibody. Moreover, cell adhesion and ROS production stimulated with MIP-1 beta or AngII were completely inhibited by fluvastatin. In our clinical study, patients with the highest quartile of MIP-1 beta showed a higher risk of stroke and cardiovascular events by a Cox proportional-hazards model. In conclusion, MIP-1 beta directly induced cell adhesion to endothelial cells through oxidative stress via PI3k-Rac1 cascades. Serum MIP-1 beta level might be a useful predictor for cerebro-cardiovascular events in hypertensive patients.Condensed abstract: We designed an in vitro investigation to examine the role of MIP-1 beta on the development of atherosclerosis, including cell adhesion involving CAMS and ROS production, compared with angiotensin II. Furthermore, we investigated the prognostic impact of MIP-1 beta on stroke and cardiovascular events in hypertensive patients in a small cohort study. (C) 2009 Elsevier Inc. All rights reserved.