Role of activated astrocytes in neuronal damage: Potential links to HIV-1-associated dementia
Role of activated astrocytes in neuronal damage: Potential links to HIV-1-associated dementia
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DOI：
10.1007/bf03036448
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发表时间：
2005-01-01
影响因子：
3.7
通讯作者：
Ghorpade, A
中科院分区：
文献类型：
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作者：
Deshpande, M;Zheng, JL;Ghorpade, A
HIV-1相关性痴呆（HAD）是HIV-1感染的重要并发症。反应性星形胶质细胞增生是HAD脑和其他中枢神经系统（CNS）疾病的关键病理特征。活化的星形胶质细胞可能在中枢神经系统炎症性疾病如HAD中起关键作用。为了检验活化的星形胶质细胞导致神经元损伤的假设，我们用HAD相关的促炎细胞因子IL-1 β刺激原代人胎儿星形胶质细胞。IL-1 β激活的星形胶质细胞诱导原代人神经元细胞凋亡和代谢活性的显著变化。FITC-缀合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活化。IL-1 β激活增强了星形胶质细胞中死亡蛋白FasL的表达，表明FasL是HAD和其他涉及神经胶质炎症的CNS疾病中观察到的神经毒性的潜在因素之一。我们的数据在这里添加到发展图片的作用，激活胶质细胞在HAD的发病机制。
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-1 beta. IL-1 beta-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-1 beta 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.