TGF-β induced by interleukin-34-stimulated microglia regulates microglial proliferation and attenuates oligomeric amyloid β neurotoxicity
TGF-β induced by interleukin-34-stimulated microglia regulates microglial proliferation and attenuates oligomeric amyloid β neurotoxicity
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DOI：
10.1016/j.neulet.2012.08.071
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发表时间：
2012-10-31
影响因子：
2.5
通讯作者：
Suzumura, Akio
中科院分区：
文献类型：
--
作者：
Ma, Di;Doi, Yukiko;Suzumura, Akio
小胶质细胞在阿尔茨海默病（Alzheimer's disease，AD）的发病机制中起重要作用。我们先前已经表明，白细胞介素-34（IL-34）通过产生胰岛素降解酶、A β降解酶和抗氧化酶血红素加氧酶-1，增强小胶质细胞增殖并诱导小胶质细胞对寡聚淀粉样蛋白β（oA β）毒性的神经保护特性。在这项研究中，我们发现IL-34剂量依赖性地诱导小胶质细胞中的TGF-β，并且TGF-β减弱神经元小胶质细胞共培养物中的oA β神经毒性。TGF-β 1受体激酶抑制剂SD 208通过IL-34增强小胶质细胞增殖并抑制IL-34处理的小胶质细胞的神经保护作用。这些发现表明，由IL-34处理的小胶质细胞产生的TGF-β是小胶质细胞增殖的负调节剂，并增强小胶质细胞的神经保护特性。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Microglia play critical roles in the pathogenesis of Alzheimer's disease (AD). We have previously shown that interleukin-34 (IL-34) enhances microglial proliferation and induces microglial neuroprotective properties against oligomeric amyloid beta (oA beta) toxicity by producing insulin degrading enzyme, an A beta degrading enzyme, and anti-oxidant enzyme heme oxygenase-1. In this study, we found that IL-34 dose-dependently induces TGF-beta in microglia, and that TGF-beta attenuates oA beta neurotoxicity in neuron microglial co-cultures. The TGF-beta 1 receptor kinase inhibitor SD208 enhances microglial proliferation by IL-34 and suppresses the neuroprotective effect of IL-34-treated microglia. These findings suggest that TGF-beta produced by IL-34-treated microglia is a negative regulator of microglial proliferation and enhances the neuroprotective property of microglia. (C) 2012 Elsevier Ireland Ltd. All rights reserved.