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Effect of methamphetamine on expression of HIV coreceptors and CC-chemokines by dendritic cells.

机译:甲基苯丙胺对树突状细胞表达HIV共受体和CC趋化因子的影响。

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摘要

The United States is currently experiencing an entangled epidemic of HIV infection and use of different drugs of abuse, especially of methamphetamine (Meth). Blood monocyte-derived dendritic cells (DC) are the first line of defense against HIV-1 infection, and are the initial target of HIV-1 infection in injection drug users. DC-SIGN present on dendritic cells is the first molecule that facilitates HIV-1 infection independent of CD4 or HIV coreceptors. AIMS: The aim of this study was to evaluate whether Meth acts as a cofactor in the pathogenesis of HIV-1 infection. MAIN METHODS: Monocyte derived DCs, obtained from normal subjects were cultured with and without Meth+/-HIV-1B, followed by analyzing the gene and protein expression by real-time quantitative polymerase chain reaction (RT-PCR) and fluorescence-activated cell-sorting analyses, respectively. KEY FINDINGS: Our results show that Meth significantly enhances HIV infection, and downregulates the gene expression of chemokines and costimulatory molecules with reciprocal upregulation of HIV coreceptors and DC-SIGN by dendritic cells. SIGNIFICANCE: Better understanding of the role of Meth in HIV-1 disease susceptibility and the mechanism through which Meth mediates its effects on HIV-1 infection may help to devise novel therapeutic strategies against HIV-1 infection in Meth using HIV-1 infected population.
机译:美国目前正遭受艾滋病毒感染和使用各种滥用药物,特别是甲基苯丙胺(甲基苯丙胺)的纠缠流行。血液单核细胞衍生的树突状细胞(DC)是抵御HIV-1感染的第一道防线,并且是注射吸毒者HIV-1感染的最初目标。树突状细胞上存在的DC-SIGN是第一个促进HIV-1感染的分子,独立于CD4或HIV共感受器。目的:这项研究的目的是评估在HIV-1感染的发病机理中,甲硫氨酸是否作为辅助因子。主要方法:在有或没有Meth +/- HIV-1B的情况下培养自正常受试者获得的单核细胞DC,然后通过实时定量聚合酶链反应(RT-PCR)和荧光激活的细胞分别进行分类分析。关键发现:我们的结果表明,甲硫氨酸可显着增强HIV感染,并通过树突状细胞相互上调HIV共受体和DC-SIGN来下调趋化因子和共刺激分子的基因表达。意义:更好地理解甲基在HIV-1疾病易感性中的作用以及介导其对HIV-1感染的影响的机制可能有助于设计使用HIV-1感染人群的新方法来治疗Meth对HIV-1的感染。

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