Interferon γ stimulates β-secretase expression and sAPPβ production in astrocytes
Interferon γ stimulates β-secretase expression and sAPPβ production in astrocytes
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DOI：
10.1016/s0006-291x(03)01270-1
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发表时间：
2003-08-08
影响因子：
3.1
通讯作者：
Mook-Jung, I
中科院分区：
文献类型：
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作者：
Hong, HS;Hwang, EM;Mook-Jung, I
神经元而非星形胶质细胞被认为是β - 淀粉样蛋白（Aβ）的主要来源，因为星形胶质细胞表达的假定β - 分泌酶（BACE）水平较低。然而，老年斑核心附近的星形胶质细胞显示出BACE蛋白表达水平升高，这表明在病理条件下星形胶质细胞可促进Aβ的产生。为了研究刺激星形胶质细胞中BACE蛋白表达的因素，我们测试了白细胞介素 - 1β（IL - 1β）和干扰素 - γ（IFN - γ）对U373MG星形细胞瘤细胞以及来自Tg2576小鼠大脑的原代星形胶质细胞培养物中BACE蛋白表达的影响。在两种细胞类型中，经过IFN - γ处理后，BACE蛋白表达和可溶性淀粉样前体蛋白β（sAPPβ）的产生显著增加，而完整的淀粉样前体蛋白（holo APP）水平没有变化。AG490是一种IFN - γ诱导的信号转导子和转录激活子（STAT）信号通路的阻断剂，它以剂量依赖的方式降低了IFN - γ诱导的BACE蛋白表达和sAPPβ的产生。这些结果表明，星形胶质细胞能够表达BACE并在某些刺激因素的作用下产生sAPPβ，而IFN - γ就是这样一种因素。（C）2003爱思唯尔公司。保留所有权利。
Neurons, but not astrocytes, are known as the major source of Abeta, because astrocytes express low levels of putative beta-secretase (BACE). Astrocytes near senile plaque cores show enhanced levels of BACE protein expression, however, suggesting that astrocytes can contribute to Abeta production under pathological conditions. To investigate factors that stimulate BACE protein expression in astrocytes, we tested the effects of interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma) on BACE protein expression in U373MG astrocytoma cells and primary astrocyte cultures from Tg2576 mouse brains. BACE protein expression and sAPPbeta production were dramatically increased, without changes in holo APP levels, following IFN-gamma treatment in both cell types. AG490, which is a blocker of IFN-gamma-induced STAT signaling, decreased IFN-gamma-induced BACE protein expression and sAPPbeta production in a dose-dependent manner. These results show that astrocytes are capable of expressing BACE and producing sAPPbeta in response to certain stimulating factors, and IFN-gamma is one such factor. (C) 2003 Elsevier Inc. All rights reserved.