Modulation of human microglia and THP-1 cell toxicity by cytokines endogenous to the nervous system
Modulation of human microglia and THP-1 cell toxicity by cytokines endogenous to the nervous system
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DOI：
10.1016/j.neurobiolaging.2004.06.012
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发表时间：
2005-05-01
影响因子：
4.2
通讯作者：
McGeer, PL
中科院分区：
文献类型：
--
作者：
Klegeris, A;Bissonnette, CJ;McGeer, PL
神经炎症过程被认为是许多退行性神经系统疾病的病理学中的重要因素。多种细胞因子影响炎症水平。在这里，我们表明，两个或两个以上的细胞因子的协同作用，需要诱导显着的人小胶质细胞和单核细胞THP-1细胞毒性对SH-SY 5 Y神经母细胞瘤细胞。这种毒性是由以下组合诱导的：干扰素-γ（IFN-γ）与肿瘤坏死因子-α（TNF-α）; IFN-γ与白细胞介素（IL）1 α或IL-1 β在TNF-α存在的情况下; IL-6与TNF-α。各种刺激组合引起的毒性并不伴随着亚硝酸盐的产生增加。潜在的抑制剂测试，IL-4下调小胶质细胞的毒性作用时，施加到THP-1细胞刺激前或刺激后24小时。IL-10不能抑制毒性，甚至可以通过转化生长因子-β（1）（TGF-β（1））和碱性成纤维细胞生长因子（bFGF）增强毒性。这些数据表明，细胞因子受体的拮抗剂，以及其细胞内途径的抑制剂可能是有效的抗炎剂。(C)2004爱思唯尔公司All rights reserved.
Neuroinflammatory processes are thought to be a significant factor in the pathology of a number of degenerative neurological diseases. A variety of cytokines influence inflammatory levels. Here we show that a cooperative action of two or more cytokines is required to induce significantly human microglial and monocytic THP-1 cell toxicity towards SH-SY5Y neuroblastoma cells. Such toxicity was induced by the following combinations: interferon-gamma (IFN-gamma) with tumor necrosis factor-alpha (TNF-alpha); IFN-gamma with interleukin (IL)1alpha or IL-1beta in the presence of TNF-alpha; and IL-6 with TNF-alpha. Toxicity induced by the various stimulatory combinations was not accompanied by an increased nitrite production. Of the potential inhibitors tested, IL-4 downregulated the toxic action of microglia when applied to THP-1 cells either before stimulation or 24 h after stimulation. Toxicity was not inhibited by IL-10, and was even enhanced by transforming growth factor-beta(1) (TGF-beta(1)) and basic fibroblast growth factor (bFGF). These data suggest that antagonists of cytokine receptors, as well as inhibitors of their intracellular pathways may be effective anti-inflammatory agents. (C) 2004 Elsevier Inc. All rights reserved.