HIV-1 gp120 up-regulation of the mu opioid receptor in TPA-differentiated HL-60 cells
HIV-1 gp120 up-regulation of the mu opioid receptor in TPA-differentiated HL-60 cells
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DOI：
10.1016/j.intimp.2006.04.018
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发表时间：
2006-09-01
影响因子：
5.6
通讯作者：
Chang, Sulie L.
中科院分区：
文献类型：
--
作者：
Beltran, Jose A.;Pallur, Anitha;Chang, Sulie L.
阿片类药物滥用已被证明会加剧免疫抑制效应和艾滋病毒感染的发病机制。mu阿片受体（mu opioid receptor， MOR）存在于巨噬细胞等免疫细胞中，介导阿片的直接免疫调节作用。HIV-1通过其表面糖蛋白gp120与靶细胞（包括巨噬细胞）表面受体结合，发挥其病理作用。gp120与巨噬细胞结合刺激细胞释放各种促炎细胞因子，包括tnf - α，其已被证明可调节MOR基因的转录。在本研究中，我们检测了HIV-1 gp120对经TPA分化为巨噬细胞样细胞的HL-60人早幼粒细胞白血病细胞MOR表达的影响。通过实时RT-PCR，我们发现gp120在转录水平上上调了tpa分化的HL-60细胞中MOR的表达。gp120诱导的MOR在这些细胞中的功能是基于吗啡对福斯克林诱导的细胞内cAMP的抑制，这是纳洛酮可逆的。暴露于gp120也刺激了tpa分化的HL-60细胞中tnf - α的释放。用tnf - α中和抗体治疗，以及用抗tnf - α受体II型（TNFR-II）抗体阻断tnf - α的作用，可抑制gp 120诱导的MOR mRNA上调。我们的数据表明，在tpa分化的HL-60细胞中，HIV-1 gp120上调MOR的机制之一是通过TNFR-II受体介导tnf - α的自分泌/旁分泌作用。(c) 2006 Elsevier B.V.版权所有
Opioid abuse has been shown to exacerbate the immunosuppressive effects and pathogenesis of HIV infection. The mu opioid receptor (MOR) is present on immune cells, such as macrophages, and mediates the direct immunomodulatory effects of opioids. Through its surface glycoprotein, gp120, HIV-1 binds to surface receptors on target cells, 'including macrophages, to exert its pathological effects. Binding of gp120 to macrophages stimulates the cells to release various pro-inflammatory cytokines, including TNF-alpha, which has been shown to regulate transcription of the MOR gene. In this study, we examined the effects of HIV-1 gp120 on MOR expression in HL-60 human promyelocytic leukemia cells differentiated into macrophage-like cells by TPA. Using real time RT-PCR, we found that exposure to gp120 up-regulated MOR expression in TPA-differentiated HL-60 cells at the transcriptional level. The functionality of the gp120-induced MOR in these cells was confirmed based on morphine's inhibition of forskolin-induced intracellular cAMP, which was naloxone reversible. Exposure to gp120 also stimulated the release of TNF-alpha from TPA-differentiated HL-60 cells. Treatment with TNF-alpha neutralizing antibody, as well as blockage of TNF-alpha's actions by anti-TNF-alpha receptor type II (TNFR-II) antibody, inhibited gp 120-induced up-regulation of MOR mRNA. Our data suggest that one of the mechanisms by which HIV-1 gp120 up-regulates the MOR in TPA-differentiated HL-60 cells is through autocrine/paracrine actions of TNF-alpha via the TNFR-II receptor. (c) 2006 Elsevier B.V. All rights reserved.