Proinflammatory cytokines and HIV-1 synergistically enhance CXCL10 expression in human astrocytes.
Proinflammatory cytokines and HIV-1 synergistically enhance CXCL10 expression in human astrocytes.
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DOI：
10.1002/glia.20801
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发表时间：
2009-05
期刊：
影响因子：
6.2
通讯作者：
Buch, Shilpa J.
中科院分区：
文献类型：
--
作者：
Williams, Rachel;Dhillon, Navneet K.;Hegde, Sonia T.;Yao, Honghong;Peng, Fuwang;Callen, Shannon;Chebloune, Yahia;Davis, Randall L.;Buch, Shilpa J.
HIV脑炎（HIV encephalitis，HIVE）是HIV相关性痴呆（HIV-associated dementia，HAD）的病理相关疾病，以星形胶质细胞增生、细胞因子/趋化因子失调和神经元变性为特征。越来越多的证据表明，炎症是积极参与HAD的发病机制。事实上，HAD/HIVE的严重程度与激活的胶质细胞的存在比与大脑中HIV感染细胞的存在和数量更密切相关。星形胶质细胞是脑内数量最多的细胞类型，为炎症介质的产生提供了重要的储存库，包括干扰素-γ诱导肽-10（CXCL 10），一种神经毒素和化学引诱物，与HAD的病理生理学有关。此外，在HIV-1感染期间，CNS组织中的促炎细胞因子IFN-γ和TNF-α也显著增加。在本研究中，我们假设宿主细胞因子和HIV-1的相互作用可能导致毒性趋化因子CXCL 10的表达增强。我们的研究结果表明，在暴露于HIV-1和促炎细胞因子的人星形胶质细胞中，CXCL 10 mRNA和蛋白的协同诱导。信号分子，包括JAK、STAT、MAPK（通过激活Erk 1/2、AKT和p38）和NF-κB被鉴定为协同诱导CXCL 10的工具。了解HIV-1和细胞因子介导的CXCL 10上调的机制有助于HAD治疗方式的发展。
HIV encephalitis (HIVE), the pathologic correlate of HIV-associated dementia (HAD) is characterized by astrogliosis, cytokine/chemokine dysregulation and neuronal degeneration. Increasing evidence suggests that inflammation is actively involved in the pathogenesis of HAD. In fact, the severity of HAD/HIVE correlates more closely with the presence of activated glial cells than with the presence and amount of HIV-infected cells in the brain. Astrocytes, the most numerous cell type within the brain, provide an important reservoir for the generation of inflammatory mediators, including interferon-γ inducible peptide-10 (CXCL10), a neurotoxin and a chemoattractant, implicated in the pathophysiology of HAD. Additionally, the pro-inflammatory cytokines, IFN-γ and TNF-α, are also markedly increased in CNS tissues during HIV-1 infection. In the present study we hypothesized that the interplay of host cytokines and HIV-1 could lead to enhanced expression of the toxic chemokine, CXCL10. Our findings demonstrate a synergistic induction of CXCL10 mRNA and protein in human astrocytes exposed to HIV-1 and the pro-inflammatory cytokines. Signaling molecules, including JAK, STATs, MAPK (via activation of Erk1/2, AKT, and p38), and NF-κB were identified as instrumental in the synergistic induction of CXCL10. Understanding the mechanisms involved in HIV-1 and cytokine mediated up-regulation of CXCL10 could aid in the development of therapeutic modalities for HAD.
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影响因子：
5.4
作者：
ADACHI, A;GENDELMAN, HE;MARTIN, MA
通讯作者：
MARTIN, MA
影响因子：
4.4
作者：
Dhillon, Navneet Kaur;Peng, Fuwang;Buch, Shilpa
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影响因子：
3.7
作者：
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DOI：
10.1073/pnas.88.8.3238
发表时间：
1991-04-01
影响因子：
11.1
作者：
GORNY, MK;XU, JY;ZOLLAPAZNER, S
通讯作者：
ZOLLAPAZNER, S
影响因子：
3.2
作者：
Albright, AV;Soldan, SS;González-Scarano, F
通讯作者：
González-Scarano, F