Human immunodeficiency virus type 1 Tat-mediated cytotoxicity of human brain microvascular endothelial cells

被引:23
|
作者
Khan, NA
Di Cello, F
Nath, A
Kim, KS
机构
[1] Johns Hopkins Univ, Sch Med, Div Pediat Infect Dis, Baltimore, MD 21287 USA
[2] Univ Kentucky, Med Ctr, Dept Neurol, Lexington, KY USA
关键词
human brain microvascular endothelial cells; IFN-gamma; PI3K; Tat; VEGFR2/KDR;
D O I
10.1080/714044480
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Human immunodeficiency virus (HIV)-1 infection is often complicated with neurologic disorders, but the pathogenesis of HIV-1 encephalopathy is incompletely understood. Tat (HIV-1 transactivator protein) is released from HIV-1 infected cells and has been detected in the sera and cerebrospinal fluid of HIV-1 -infected patients. Tat, along with increased inflammatory cytokines such as interferon-gamma (IFN-gamma), have been implicated in the pathogenesis of HIV-1 -associated blood-brain barrier dysfunction. The present study examined the effects of Tat and IFN-gamma on human brain microvascular endothelial cells (HB-MECs), which constitute the blood-brain barrier. Tat produced cytotoxicity of HBMECs, but required IFN-gamma. IFN-gamma treatment of HBMECs up-regulates vascular endothelial growth factor receptor-2 (VEGFR2/KDR), which is known to be the receptor for Tat. Tat activated KDR in the presence of IFN-gamma, and Tat-mediated cytopathic changes involve its interaction with KDR and phosphatidylinositol 3-kinase (PI3K). Further understanding and characterization of Tat-HBMEC interactions should help us understand HIV-1 neuropathogenesis and develop strategies to prevent HIV-1 encephalopathy.
引用
收藏
页码:584 / 593
页数:10
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