Serum amyloid a differentially activates microglia and astrocytes via the PI3K pathway.
Serum amyloid a differentially activates microglia and astrocytes via the PI3K pathway.
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DOI：
10.3233/jad-130818
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发表时间：
2013-10
期刊：
影响因子：
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通讯作者：
Yang Yu;Jin Liu;Shuqin Li;Lei Peng;R. Ye
中科院分区：
文献类型：
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作者：
Yang Yu;Jin Liu;Shuqin Li;Lei Peng;R. Ye
脑内的小胶质细胞和星形胶质细胞在阿尔茨海默病（AD）的发生和发展中起着重要作用。血清淀粉样蛋白A（SAA）是一种主要的急性时相蛋白，在大脑中产生的局部和共定位与老年斑在AD患者。我们调查SAA是否在AD的发展中起作用。MTT法检测原代培养的小胶质细胞和星形胶质细胞的活力，并进行细胞周期和凋亡分析。将培养的小胶质细胞和星形胶质细胞用1 μM SAA刺激不同时间（2、4、6、12 h）或用1 μM SAA处理（有或没有MAPK或PI 3 K抑制剂预处理15 min）。提取总RNA用于qPCR分析。SAA诱导原代小胶质细胞的形态学改变，但不诱导星形胶质细胞。有趣的是，SAA通过抑制小胶质细胞的凋亡而增加其活力，并通过诱导G1期细胞阻滞而降低星形胶质细胞的活力。SAA处理增加了IL-6、TNF-α、IL 12 p40、IL 23 p19和IL-10的mRNA水平，在小胶质细胞中的效力高于星形胶质细胞。然而，SAA诱导更多的iNOSmRNA在星形胶质细胞比在小胶质细胞。SAA通过激活两种胶质细胞中的PI 3 K通路诱导这些细胞因子和iNOS表达，但选择性地激活小胶质细胞中的JNK通路和星形胶质细胞中的NF-κB通路。这些结果表明，SAA可以刺激小胶质细胞和星形胶质细胞中不同的反应表型，SAA部分通过PI 3 K途径在这两种胶质细胞中不同地调节细胞活力。
Microglia and astrocytes in the brain play an important role in the development and progression of Alzheimer's disease (AD). Serum amyloid A (SAA) is a major acute-phase protein produced locally in the brain and colocalizes with senile plaques in AD patients. We investigated whether SAA plays a role in the development of AD. The viability of cultured primary microglia and astrocytes was measured by MTT; cell cycle and apoptosis analysis was also conducted. Cultured microglia and astrocytes were stimulated with 1 μM SAA for different periods of time (2, 4, 6, 12 h) or treated with 1 μM SAA with or without 15 min pretreatment of MAPK or PI3K inhibitors. Total RNA was extracted for qPCR analysis. SAA induced morphological changes of primary microglia but not astrocytes. Interestingly, SAA increased the viability of microglia by inhibiting their apoptosis and reduced the viability of astrocytes by inducing G1 cell cycle arresting. SAA treatment increased the mRNA levels of IL-6, TNF-α, IL12p40, IL23p19, and IL-10, with higher potency in microglia than in astrocytes. However, SAA induced more iNOS mRNA in astrocytes than in microglia. SAA induced these cytokines and iNOS expression by activating the PI3K pathway in both glial cells, but selectively activated the JNK pathway in microglia and the NF-κB pathway in astrocytes. These results suggest that SAA can stimulate a different reactive phenotype in microglia and astrocytes, and SAA regulates cell viability differently in these two glial cells in part through the PI3K pathway.