HIV-1和白细胞介素-1β通过核因子κB途径调节人星形胶质细胞中Fas配体的表达。

HIV-1 and IL-1 beta regulate Fas ligand expression in human astrocytes through the NF-kappa B pathway.

作者信息

Ghorpade A, Holter S, Borgmann K, Persidsky R, Wu L

机构信息

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-5215, USA.

出版信息

J Neuroimmunol. 2003 Aug;141(1-2):141-9. doi: 10.1016/s0165-5728(03)00222-4.

DOI:10.1016/s0165-5728(03)00222-4

PMID:12965265

Abstract

Reactive astrogliosis is a prominent pathological feature of HIV-1-associated dementia (HAD). We hypothesized that in HAD, astrocytes activated with proinflammatory stimuli such as IL-1beta express Fas ligand (FasL), a death protein. IL-1beta and HIV-1-activated astrocytes expressed FasL mRNA and protein. Luciferase reporter constructs showed that IL-1beta and HIV-1 upregulated FasL promoter activity (p<0.001). The NF-kappaB pathway was involved as shown by inhibition with SN50 and dominant negative IkappaBalpha mutants. Brain extracts from HAD patients had significantly elevated FasL levels compared to HIV-seropositive (p<0.001) and seronegative individuals (p<0.01). We propose that astrocyte expression of FasL may participate in neuronal injury in HAD.

摘要

反应性星形胶质细胞增生是HIV-1相关痴呆（HAD）的一个突出病理特征。我们推测，在HAD中，被白细胞介素-1β等促炎刺激激活的星形胶质细胞表达Fas配体（FasL），一种死亡蛋白。白细胞介素-1β和HIV-1激活的星形胶质细胞表达FasL mRNA和蛋白。荧光素酶报告基因构建体显示，白细胞介素-1β和HIV-1上调FasL启动子活性（p<0.001）。如用SN50和显性负性IκBα突变体抑制所示，NF-κB途径参与其中。与HIV血清阳性个体（p<0.001）和血清阴性个体（p<0.01）相比，HAD患者的脑提取物中FasL水平显著升高。我们提出，星形胶质细胞FasL的表达可能参与了HAD中的神经元损伤。