Central nervous system dysfunction is commonly observed in children with HIV-1 infection, but the mechanisms whereby HIV-1 causes encephalopathy are not completely understood. We have previously shown that human brain microvascular endothelial cells (HBMEC) from children are responsive to gp120 derived from X4 HIV-1 by increasing expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule-1. However, the mechanisms involved in gp120-mediated up-regulation of cell adhesion molecule expression is unclear. In the present study, we found that gp120 derived from both X4 and R5 HIV-1 induced increased expression of ICAM-1 on HBMEC, but the degree of this up-regulation differed among the various HBMEC isolates. The up-regulation of ICAM-1 was inhibited by anti-CD4 antibodies as well as by specific antibodies directed against chemokine receptors and small-molecule coreceptor inhibitors. Anti-CD4 antibodies inhibited the increase in ICAM-1 expression mediated by gp120 derived from X4 and R5 HIV-1, whereas antibodies against chemokine receptors displayed a differential inhibition depending on the source of gp120. Both X4 and R5 gp120-induced ICAM-1 expression was sensitive to pertussis toxin and involved the nuclear factor-kB pathway. These findings indicate a direct involvement of CD4 and a differential involvement of chemokine receptors in the activation of pediatric HBMEC by X4 and R5 gp120. The activation of brain endothelium of children by HIV-1 protein gp120 by way of CD4 and chemokine receptors may have implications for the pathogenesis of HIV-1 encephalopathy in the pediatric population.

中文翻译：

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HIV-1 gp120 对人脑内皮细胞细胞间粘附分子-1 的诱导作用：CD4 和趋化因子辅助受体的作用。

中枢神经系统功能障碍在感染 HIV-1 的儿童中很常见，但 HIV-1 引起脑病的机制尚不完全清楚。我们之前已经表明，儿童的人脑微血管内皮细胞 (HBMEC) 通过增加细胞间粘附分子 (ICAM)-1 和血管细胞粘附分子-1 的表达，对源自 X4 HIV-1 的 gp120 有反应。然而，gp120 介导的细胞粘附分子表达上调所涉及的机制尚不清楚。在本研究中，我们发现来自 X4 和 R5 HIV-1 的 gp120 诱导 HBMEC 上 ICAM-1 的表达增加，但这种上调的程度在不同的 HBMEC 分离株中不同。ICAM-1 的上调受到抗 CD4 抗体以及针对趋化因子受体和小分子辅助受体抑制剂的特异性抗体的抑制。抗 CD4 抗体抑制由源自 X4 和 R5 HIV-1 的 gp120 介导的 ICAM-1 表达增加，而针对趋化因子受体的抗体显示出不同的抑制作用，具体取决于 gp120 的来源。X4 和 R5 gp120 诱导的 ICAM-1 表达对百日咳毒素敏感并涉及核因子-kB 通路。这些发现表明 CD4 直接参与和趋化因子受体不同地参与 X4 和 R5 gp120 对儿科 HBMEC 的激活。