Potentiation of HIV-1 expression in microglial cells by nicotine: involvement of transforming growth factor-beta 1.
Potentiation of HIV-1 expression in microglial cells by nicotine: involvement of transforming growth factor-beta 1.
复制标题
尼古丁增强小胶质细胞中 HIV-1 表达：转化生长因子-β 1 的参与。
DOI：
10.1007/s11481-007-9098-7
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Peterson,PhillipK
中科院分区：
文献类型：
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作者：
Rock,RBryan;Gekker,Genya;Aravalli,RajagopalN;Hu,Shuxian;Sheng,WenS;Peterson,PhillipK
HIV-1感染和尼古丁成瘾是全球公共卫生危机。在中枢神经系统中，HIV-1会导致一种毁灭性的神经退行性疾病。众所周知，小胶质细胞在HIV-1的神经发病机制中起着关键作用，滥用药物不仅有助于这种药物的传播，而且可能促进这些脑巨噬细胞中的病毒表达。尼古丁已被证明可以刺激体外感染的肺泡巨噬细胞产生HIV-1，HIV-1蛋白gp 120与尼古丁受体结合。在这项研究中，我们证明了烟碱乙酰胆碱受体mRNA的组成型表达在原代人小胶质细胞，并表明，尼古丁的小胶质细胞的预处理增加HIV-1的表达，以浓度依赖性的方式，作为测量培养上清液中的p24抗原水平。我们还发现尼古丁强烈改变了HIV-1感染的小胶质细胞的基因表达谱，并且转化生长因子-β1参与尼古丁增强HIV-1的表达。
HIV-1 infection and nicotine addiction are global public health crises. In the central nervous system, HIV-1 causes a devastating neurodegenerative disease. It is well recognized that microglial cells play a pivotal role in the neuropathogenesis of HIV-1 and that drugs of abuse not only contribute to the spread of this agent but may facilitate viral expression in these brain macrophages. Nicotine has been shown to stimulate the production of HIV-1 by in vitro-infected alveolar macrophages, and the HIV-1 protein gp120 binds to nicotinic receptors. In this study, we demonstrated the constitutive expression of nicotinic acetylcholine receptor mRNA in primary human microglial cells and showed that the pretreatment of microglia with nicotine increased HIV-1 expression in a concentration-dependent manner, as measured by p24 antigen levels in culture supernatants. We also found that nicotine robustly altered the gene expression profile of HIV-1-infected microglia and that the transforming growth factor-β1 is involved in the enhanced expression of HIV-1 by nicotine.