An Xiao-Qun, Xi Wei, Gu Chen-Yun, Huang Xiao
MD, Department of Psychiatry, Yangpu District Mental Health Center of Shanghai, 585 Jungong Road, Shanghai (200090), China.
MD, Department of Psychological Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai (200032), China.
Med Sci (Paris). 2018 Oct;34 Focus issue F1:116-120. doi: 10.1051/medsci/201834f120. Epub 2018 Nov 7.
The dysregulation of neuro-inflammation is one of the attributes of the pathogenesis of Alzheimer's disease (AD). Over-expression of complement proteins co-localizes with neurofibrillary tangles, thereby indicating that a complement system may be involved in neuro-inflammation. Here, we report the influence of complement activation on the neuro-inflammation using a microglial cell line.
first, we performed a cytotoxic assay using the microglial cells BV-2. Second, after treatment of BV-2 cells with Aβ and/ or C5a, the anaphylatoxin derived from C5, we determined the expression levels of the pro-inflammatory factors TNF-α, IL-1β, and IL-6. Finally, we explored whether this neuroinflammatory response was mediated by JAK/ STAT3 signaling.
C5a had an enhanced effect on the neural cell viability of BV-2 cells treated with Aβ. In addition, C5a also increased the Aβ-induced neuro-inflammatory response, and these effects were blocked by the C5aR antagonist, PMX205. Finally, we demonstrated that the neuro-inflammatory responses induced by Aβ and C5a were mediated through JAK/STAT3 signaling. By blocking this pathway with an antagonist, AG490, the expression of TNF-α, IL-1β, and IL-6 was alleviated.
The complement protein C5a could exaggerate the Aβ-induced neuroinflammatory response in microglia, and C5aR may be a potential therapeutic tool for AD treatment.
神经炎症调节异常是阿尔茨海默病（AD）发病机制的特征之一。补体蛋白的过度表达与神经原纤维缠结共定位，从而表明补体系统可能参与神经炎症。在此，我们报道使用小胶质细胞系研究补体激活对神经炎症的影响。
首先，我们使用小胶质细胞BV-2进行细胞毒性测定。其次，在用Aβ和/或源自C5的过敏毒素C5a处理BV-2细胞后，我们测定促炎因子TNF-α、IL-1β和IL-6的表达水平。最后，我们探究这种神经炎症反应是否由JAK/STAT3信号介导。
C5a对用Aβ处理的BV-2细胞的神经细胞活力有增强作用。此外，C5a还增加了Aβ诱导的神经炎症反应，并且这些作用被C5aR拮抗剂PMX205阻断。最后，我们证明Aβ和C5a诱导的神经炎症反应是通过JAK/STAT3信号介导的。通过用拮抗剂AG490阻断该途径，TNF-α、IL-1β和IL-6的表达得到缓解。
补体蛋白C5a可加剧小胶质细胞中Aβ诱导的神经炎症反应，并且C5aR可能是AD治疗的潜在治疗工具。
