IL-10 mediated by herpes simplex virus vector reduces neuropathic pain induced by HIV gp120 combined with ddC in rats.
IL-10 mediated by herpes simplex virus vector reduces neuropathic pain induced by HIV gp120 combined with ddC in rats.
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DOI：
10.1186/1744-8069-10-49
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发表时间：
2014-07-30
期刊：
影响因子：
3.3
通讯作者：
Hao S
中科院分区：
文献类型：
--
作者：
Zheng W;Huang W;Liu S;Levitt RC;Candiotti KA;Lubarsky DA;Hao S
HIV 相关感觉神经病变影响超过 50% 的 HIV 患者，是 HIV 感染和高效抗逆转录病毒治疗 (HAART) 的常见周围神经并发症。有证据表明，疼痛性 HIV 感觉神经病受到神经炎症事件的影响，包括促炎分子、MAP 激酶、肿瘤坏死因子-α (TNFα)、基质细胞衍生因子 1-α (SDF1α) 和 C-X-C 趋化因子受体 4 型 (CXCR4)。然而，痛苦的艾滋病毒感觉神经病的确切机制尚不清楚，这阻碍了我们开发有效治疗方法的能力。在这项研究中，我们研究了抑制促炎因子是否可以减轻 HIV 相关的神经性疼痛状态。神经性疼痛是由外周 HIV 外壳蛋白 gp120 与 2',3'-双脱氧胞苷（ddC，核苷逆转录酶抑制剂 (NRTI) 之一）结合诱导的。使用冯弗雷长丝纤维测试机械阈值。将表达白细胞介素 10 (IL10) 的非复制性单纯疱疹病毒 (HSV) 载体接种到大鼠的后爪中。使用蛋白质印迹法检查腰脊髓和 L4/5 背根神经节 (DRG) 中 TNFα、SDF1α 和 CXCR4 的表达。 HSV 载体介导的 IL-10 表达导致机械阈值显着升高。 HSV 载体介导的 IL-10 表达的抗异常疼痛作用持续超过 3 周。与对照载体相比，接种表达IL-10的HSV载体的大鼠的机械阈值的效应-时间曲线下面积(AUC)增加，表明IL-10载体的抗伤害作用。表达 IL-10 的 HSV 载体还同时逆转了 2 周和/或 4 周时腰椎背角和/或 DRG 中 gp120 诱导的 p-p38、TNFα、SDF1α 和 CXCR4 的上调。阻断这些促炎分子的信号传导能够减轻 HIV 相关的神经性疼痛，这为使用基因疗法治疗 HIV 相关的神经性疼痛提供了一种基于机制的新方法。
HIV-associated sensory neuropathy affects over 50% of HIV patients and is a common peripheral nerve complication of HIV infection and highly active antiretroviral therapy (HAART). Evidence shows that painful HIV sensory neuropathy is influenced by neuroinflammatory events that include the proinflammatory molecules, MAP Kinase, tumor necrosis factor-α (TNFα), stromal cell-derived factor 1-α (SDF1α), and C-X-C chemokine receptor type 4 (CXCR4). However, the exact mechanisms of painful HIV sensory neuropathy are not known, which hinders our ability to develop effective treatments. In this study, we investigated whether inhibition of proinflammatory factors reduces the HIV-associated neuropathic pain state. Neuropathic pain was induced by peripheral HIV coat protein gp120 combined with 2′,3′-dideoxycytidine (ddC, one of the nucleoside reverse transcriptase inhibitors (NRTIs)). Mechanical threshold was tested using von Frey filament fibers. Non-replicating herpes simplex virus (HSV) vectors expressing interleukin 10 (IL10) were inoculated into the hindpaws of rats. The expression of TNFα, SDF1α, and CXCR4 in the lumbar spinal cord and L4/5 dorsal root ganglia (DRG) was examined using western blots. IL-10 expression mediated by the HSV vectors resulted in a significant elevation of mechanical threshold. The anti-allodynic effect of IL-10 expression mediated by the HSV vectors lasted more than 3 weeks. The area under the effect-time curves (AUC) in mechanical threshold in rats inoculated with the HSV vectors expressing IL-10, was increased compared with the control vectors, indicating antinociceptive effect of the IL-10 vectors. The HSV vectors expressing IL-10 also concomitantly reversed the upregulation of p-p38, TNFα, SDF1α, and CXCR4 induced by gp120 in the lumbar spinal dorsal horn and/or the DRG at 2 and/or 4 weeks. The blocking of the signaling of these proinflammatory molecules is able to reduce HIV-related neuropathic pain, which provide a novel mechanism-based approach to treating HIV-associated neuropathic pain using gene therapy.
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影响因子：
3.7
作者：
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影响因子：
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影响因子：
3.3
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影响因子：
6.4
作者：
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影响因子：
9.9
作者：
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