Neuronal apoptosis is mediated by CXCL10 overexpression in simian human immunodeficiency virus encephalitis
Neuronal apoptosis is mediated by CXCL10 overexpression in simian human immunodeficiency virus encephalitis
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DOI：
10.1016/s0002-9440(10)63714-5
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发表时间：
2004-05-01
影响因子：
6
通讯作者：
Buch, S
中科院分区：
文献类型：
--
作者：
Sui, YJ;Potula, R;Buch, S
炎症介质在包括获得性免疫缺陷综合征痴呆在内的几种神经退行性疾病的病理生理中起着至关重要的作用。在本研究中，我们确定了CXCL10在大脑中的过表达与人类免疫缺陷病毒痴呆之间的联系，并证明了趋化因子CXCL10及其受体CXCR3在猿类人类免疫缺陷病毒脑炎的猕猴大脑神经元中存在。利用人类胎儿大脑培养物，我们发现用SHIV89.6P或病毒gp120处理这些细胞可诱导神经元中CXCL10的表达。经趋化因子处理的培养神经元膜通透性增加，随后通过激活caspase-3发生细胞凋亡。我们在患有脑病的人类和猕猴大脑切片中证实了这些发现的相关性，表明表达CXCL10的神经元也表达caspase-3。
Inflammatory mediators play a crucial role in the pathophysiology of several neurodegenerative diseases including acquired immune deficiency syndrome dementia complex. In the present study we identified a link between CXCL10 overexpression in the brain and human immunodeficiency virus dementia and demonstrated the presence of the chemokine CXCL10 and its receptor, CXCR3, in the neurons in the brains of macaques with simian human immunodeficiency virus encephalitis. Using human fetal brain cultures, we showed that treatment of these cells with either SHIV89.6P or viral gp120 resulted in induction of CXCL10 in neurons. Cultured neurons treated with the chemokine developed increased membrane permeability followed by apoptosis via activation of caspase-3. We confirmed the relevance of these findings in sections of human and macaque brains with encephalopathy demonstrating that neurons expressing CXCL10 also expressed caspase-3.