IRF-8 is Involved in Amyloid-β1-40 (Aβ1-40)-induced Microglial Activation: a New Implication in Alzheimer's Disease

被引：16
作者：
Zeng, Qinggan [1 ]
Man, Rongyong [2 ]
Luo, Yifeng [1 ]
Zeng, Ling [2 ]
Zhong, Yushi [2 ]
Lu, Bingxun [1 ]
Wang, Xiaofeng [1 ]
机构：
[1] Southern Med Univ, Affiliated Hosp 3, Dept Neurol, 183 Zhongshan Rd West, Guangzhou 510630, Guangdong, Peoples R China
[2] Univ South China, Peoples Hosp Huaihua 1, Dept Neurol, 144 Jinxi Rd South, Huaihua 418000, Peoples R China
来源：
JOURNAL OF MOLECULAR NEUROSCIENCE | 2017年 / 63卷 / 02期
关键词：
Alzheimer's disease; Interferon regulatory factor-8 (IRF-8); Microglia; Neuroinflammation; Amyloid-beta; AMYLOID-BETA PEPTIDES; TRANSCRIPTION FACTOR; EXPRESSION; BINDING; PATHWAY;
D O I：
10.1007/s12031-017-0966-1
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
It is well known that extracellular deposition of amyloid-beta (A beta) peptide and microglia-mediated neuroinflammation are major hallmarks of Alzheimer's disease (AD). Interferon regulatory factor-8 (IRF-8), an important transcription factor of the IRF family, is highly restricted in microglia in brains. The expression pattern and function of IRF-8 in AD need to be elucidated in order to provide novel therapies for the treatment of AD. In this study, our results indicated that expression of IRF-8 is significantly elevated in the brains and microglia of AD transgenic model Tg2576 mice. Notably, in vitro cell culture and reporter luciferase assay show that A beta(1-40) treatment promotes expression of IRF-8 at the transcriptional level. Silencing of IRF-8 in microglia abolished A beta(1-40)-induced elevation in typical activated microglia-related genes, including the microglial innate response receptor toll-like receptor 2 (TLR2), the chemotaxis gene purinergic receptor P2Y12R, and the proinflammatory cytokine IL-1 beta. However, overexpression of IRF-8 exacerbated the elevated expression of these proteins. Finally, the JAK2/STAT-1 pathway was found to mediate A beta(1-40)-induced elevation of IRF-8. Overall, this is the first time to report that IRF-8 is involved in microglial activation and neuroinflammation in AD.
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页码：159 / 164
页数：6
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