Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
Neurosci Lett. 2012 Oct 31;529(1):86-91. doi: 10.1016/j.neulet.2012.08.071. Epub 2012 Sep 7.
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 β (oAβ) toxicity by producing insulin degrading enzyme, an Aβ degrading enzyme, and anti-oxidant enzyme heme oxygenase-1. In this study, we found that IL-34 dose-dependently induces TGF-β in microglia, and that TGF-β attenuates oAβ neurotoxicity in neuron microglial co-cultures. The TGF-β 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-β produced by IL-34-treated microglia is a negative regulator of microglial proliferation and enhances the neuroprotective property of microglia.
小胶质细胞在阿尔茨海默病（AD）的发病机制中发挥着关键作用。我们之前的研究表明，白细胞介素-34（IL-34）通过产生胰岛素降解酶、Aβ 降解酶和抗氧化酶血红素加氧酶-1，增强小胶质细胞的增殖，并诱导小胶质细胞对寡聚淀粉样β（oAβ）毒性的神经保护特性。在这项研究中，我们发现 IL-34 可剂量依赖性地诱导小胶质细胞产生 TGF-β，而 TGF-β 可减弱神经元-小胶质细胞共培养物中的 oAβ 神经毒性。TGF-β1 受体激酶抑制剂 SD208 增强了 IL-34 诱导的小胶质细胞增殖，并抑制了 IL-34 处理的小胶质细胞的神经保护作用。这些发现表明，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，并增强了小胶质细胞的神经保护特性。
