Methamphetamine Modulates DC-SIGN Expression by Mature Dendritic Cells

Methamphetamine Modulates DC-SIGN Expression by Mature Dendritic Cells
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DOI:
10.1007/s11481-006-9027-1
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发表时间:
2006-09-01
影响因子:
6.2
通讯作者:
Reynolds, Jessica L.
Reynolds, Jessica L.
中科院分区:
医学3区
文献类型:
--
作者:
Nair, Madhavan P. N.;Mahajan, Supriya;Reynolds, Jessica L.

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我们报告,甲基苯丙胺(甲基)可能作为辅助因子在人类免疫缺陷病毒(HIV)-1的发病机制,通过增加树突状细胞(DC)特异性细胞间粘附分子-3(ICAM-3)抓非整合素(DC-SIGN)的表达。从正常受试者中获得的成熟DC(MDCs),用metha培养,分别通过实时定量聚合酶链反应和荧光激活细胞分选分析显示DC-SIGN基因和蛋白表达的上调。此外,多巴胺D1受体拮抗剂(SCH 23390)和D1受体(D1 R)特异性小干扰RNA可逆转这些甲基诱导的效应,表明甲基诱导的效应是通过这些受体介导的。此外,甲基与HIV-1肽gp 120协同上调MDCs的DC-SIGN基因表达。这些数据是第一个证据表明,冰毒上调MDCs上DC-SIGN的表达。更好地了解DC-SIGN在HIV-1感染中的作用可能有助于设计新的治疗策略,以对抗吸毒人群中HIV-1疾病的进展。
We report that methamphetamine (meth) may act as cofactor in human immunodeficiency virus (HIV)-1 pathogenesis by increasing dendritic cell (DC)-specific intercellular adhesion molecule-3 (ICAM-3) grabbing nonintegrin (DC-SIGN) expression on DCs. Mature DCs (MDCs), obtained from normal subjects, cultured with meth show an up-regulation of DC-SIGN gene and protein expression as analyzed by real-time quantitative polymerase chain reaction and fluorescence-activated cell-sorting analyses, respectively. Furthermore, these meth-induced effects were reversed by a dopamine D1 receptor antagonist (SCH 23390) and small interfering RNA specific to the D1 receptor (D1R) demonstrating that meth-induced effects are mediated through these receptors. Furthermore, meth in synergy with the HIV-1 peptide gp120 up-regulates DC-SIGN gene expression by MDCs. These data are the first evidence that meth up-regulates the expression of DC-SIGN on MDCs. A better understanding of the role of DC-SIGN in HIV-1 infection may help to design novel therapeutic strategies against the progression of HIV-1 disease in the drug-using population.