Deshpande M, Zheng J, Borgmann K, Persidsky R, Wu L, Schellpeper C, Ghorpade A
Laboratories of Cellular Neuroimmunology and Neurotoxicology, Center for Neurovirology and Neurodegenerative Disorders, Department of Pharmacology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5215, USA.
Neurotox Res. 2005;7(3):183-92. doi: 10.1007/BF03036448.
HIV-1-associated dementia (HAD) is an important complication of HIV-1 infection. Reactive astrogliosis is a key pathological feature in HAD brains and in other central nervous system (CNS) diseases. Activated astroglia may play a critical role in CNS inflammatory diseases such as HAD. In order to test the hypothesis that activated astrocytes cause neuronal injury, we stimulated primary human fetal astrocytes with HAD-relevant pro-inflammatory cytokine IL-1beta. IL-1beta-activated astrocytes induced apoptosis and significant changes in metabolic activity in primary human neurons. An FITC-conjugated pan-caspase inhibitor peptide FITC-VAD-FMK was used for confirming caspase activation in neurons. IL-1beta activation enhanced the expression of death protein FasL in astrocytes, suggesting that FasL is one of the potential factors responsible for neurotoxicity observed in HAD and other CNS diseases involving glial inflammation. Our data presented here add to the developing picture of role of activated glia in HAD pathogenesis.
HIV-1相关性痴呆（HAD）是HIV-1感染的一种重要并发症。反应性星形胶质细胞增生是HAD脑部以及其他中枢神经系统（CNS）疾病的关键病理特征。活化的星形胶质细胞可能在诸如HAD等CNS炎症性疾病中起关键作用。为了验证活化的星形胶质细胞导致神经元损伤这一假说，我们用与HAD相关的促炎细胞因子IL-1β刺激原代人胎儿星形胶质细胞。IL-1β活化的星形胶质细胞诱导原代人神经元发生凋亡并使其代谢活性发生显著变化。一种异硫氰酸荧光素（FITC）偶联的泛半胱天冬酶抑制剂肽FITC-VAD-FMK用于确认神经元中的半胱天冬酶激活。IL-1β激活增强了星形胶质细胞中死亡蛋白FasL的表达，表明FasL是在HAD以及其他涉及胶质细胞炎症的CNS疾病中观察到的神经毒性的潜在因素之一。我们在此展示的数据进一步完善了活化胶质细胞在HAD发病机制中作用的认识。
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