Dimethyl fumarate modulation of immune and antioxidant responses: application to HIV therapy.
Dimethyl fumarate modulation of immune and antioxidant responses: application to HIV therapy.
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DOI：
10.1615/critrevimmunol.2013007247
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发表时间：
2013
影响因子：
1.3
通讯作者：
Kolson DL
中科院分区：
文献类型：
--
作者：
Gill AJ;Kolson DL
慢性免疫激活和氧化应激在人类免疫缺陷病毒（HIV）感染，抗逆转录病毒药物治疗的个人的持续存在是充分预防HIV疾病进展的主要障碍。免疫调节剂和抗氧化剂富马酸二甲酯（DMF）可有效治疗免疫介导的疾病，也可用于限制HIV疾病进展。DMF及其活性代谢产物富马酸单甲酯（MMF）的相关作用包括诱导Th 1 → Th 2淋巴细胞转换、抑制促炎细胞因子信号传导、抑制NF-κB核转位、抑制树突状细胞成熟、抑制淋巴细胞和内皮细胞粘附分子表达以及诱导Nrf 2依赖性抗氧化反应元件（ARE）和效应基因。与这些作用相关的是人类银屑病皮肤病变中淋巴细胞和单核细胞浸润减少以及啮齿动物中免疫介导的脱髓鞘脑病变，这证实了强效的全身和中枢神经系统（CNS）作用。此外，DMF和MMF在体外限制巨噬细胞中的HIV感染，尽管机制未知。最后，DMF和MMF还抑制HIV感染的巨噬细胞产生神经毒素，这会导致CNS神经变性。因此，DMF可通过有效抑制免疫活化、氧化应激、HIV复制和巨噬细胞相关神经元损伤，预防HIV感染中的全身和CNS并发症。
The persistence of chronic immune activation and oxidative stress in human immunodeficiency virus (HIV)-infected, antiretroviral drug-treated individuals are major obstacles to fully preventing HIV disease progression. The immune modulator and antioxidant dimethyl fumarate (DMF) is effective in treating immune-mediated diseases and it also has potential applications to limiting HIV disease progression. Among the relevant effects of DMF and its active metabolite monomethyl fumarate (MMF) are induction of a Th1 → Th2 lymphocyte shift, inhibition of pro-inflammatory cytokine signaling, inhibition of NF-κB nuclear translocation, inhibition of dendritic cell maturation, suppression of lymphocyte and endothelial cell adhesion molecule expression, and induction of the Nrf2-dependent antioxidant response element (ARE) and effector genes. Associated with these effects are reduced lymphocyte and monocyte infiltration into psoriatic skin lesions in humans and immune-mediated demyelinating brain lesions in rodents, which confirms potent systemic and central nervous system (CNS) effects. In addition, DMF and MMF limit HIV infection in macrophages in vitro, albeit by unknown mechanisms. Finally, DMF and MMF also suppress neurotoxin production from HIV-infected macrophages, which drives CNS neurodegeneration. Thus, DMF might protect against systemic and CNS complications in HIV infection through its effective suppression of immune activation, oxidative stress, HIV replication, and macrophage-associated neuronal injury.
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影响因子：
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作者：
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