HIV-1 Tat protein-induced VCAM-1 expression in human pulmonary artery endothelial cells and its signaling
HIV-1 Tat protein-induced VCAM-1 expression in human pulmonary artery endothelial cells and its signaling
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DOI：
10.1152/ajplung.00200.2004
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发表时间：
2005-08-01
影响因子：
4.9
通讯作者：
Krishnaswamy, G
中科院分区：
文献类型：
--
作者：
Liu, K;Chi, DS;Krishnaswamy, G
人类免疫缺陷病毒（HIV）感染激活内皮细胞后细胞粘附分子的表达与动脉粥样硬化性血管病变的发生有关。我们推测，诱导血管细胞粘附分子-1（VCAM-1）的HIV-1达特蛋白在内皮细胞可能代表一个早期事件，可以最终在炎症细胞招聘和血管损伤。我们确定了HIV-1达特蛋白在人肺动脉内皮细胞（HPAEC）VCAM-1表达中的作用。HIV-1达特蛋白处理显著增加HPAEC中VCAM-1的细胞表面表达。RT-PCR结果显示，HIV-1达特蛋白能促进VCAM-1 mRNA的表达。NF-κ B抑制剂吡咯烷二硫代氨基甲酸酯（PDTC）和p38 MAPK抑制剂SB-203580可消除HIV-1达特蛋白诱导的VCAM-1表达。此外，HIV-1达特蛋白增强NF-κ B B的DNA结合活性，促进NF-κ B B亚基p65的核转位，并增加活性氧（ROS）的产生。与VCAM-1表达相似，PDTC和SB-203580可消除HIV-1达特蛋白诱导的NF-κ B活化和ROS生成。这些数据表明HIV-1达特蛋白能够诱导HPAEC中VCAM-1的表达，这可能代表HIV诱导的血管/肺损伤中的关键早期分子事件。这些数据还表明，HIV-1达特蛋白诱导VCAM-1表达的分子机制可能涉及ROS产生、p38 MAPK激活和NF-κ B B易位，这些都是肺内皮细胞活化的特征。
Expression of cell adhesion molecule in endothelial cells upon activation by human immunodeficiency virus (HIV) infection is associated with the development of atherosclerotic vasculopathy. We postulated that induction of vascular cell adhesion molecule-1 (VCAM-1) by HIV-1 Tat protein in endothelial cells might represent an early event that could culminate in inflammatory cell recruitment and vascular injury. We determined the role of HIV-1 Tat protein in VCAM-1 expression in human pulmonary artery endothelial cells (HPAEC). HIV-1 Tat protein treatment significantly increased cell-surface expression of VCAM-1 in HPAEC. Consistently, mRNA expression of VCAM-1 was also increased by HIV-1 Tat protein as measured by RT-PCR. HIV-1 Tat protein-induced VCAM-1 expression was abolished by the NF-kappa B inhibitor pyrrolidine dithiocarbamate ( PDTC) and the p38 MAPK inhibitor SB-203580. Furthermore, HIV-1 Tat protein enhanced DNA binding activity of NF-kappa B, facilitated nuclear translocation of NF-kappa B subunit p65, and increased production of reactive oxygen species (ROS). Similarly to VCAM-1 expression, HIV-1 Tat protein-induced NF-kappa B activation and ROS generation were abrogated by PDTC and SB-203580. These data indicate that HIV-1 Tat protein is able to induce VCAM-1 expression in HPAEC, which may represent a pivotal early molecular event in HIV- induced vascular/pulmonary injury. These data also suggest that the molecular mechanism underlying the HIV-1 Tat protein-induced VCAM-1 expression may involve ROS generation, p38 MAPK activation, and NF-kappa B translocation, which are the characteristics of pulmonary endothelial cell activation.