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

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Abstract

It is well known that extracellular deposition of amyloid-β (Aβ) 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 Aβ1–40 treatment promotes expression of IRF-8 at the transcriptional level. Silencing of IRF-8 in microglia abolished Aβ1–40-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-1β. However, overexpression of IRF-8 exacerbated the elevated expression of these proteins. Finally, the JAK2/STAT-1 pathway was found to mediate Aβ1–40-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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Funding Information

This study was supported by the Science and Technology Planning Project of Guangdong Province, China (2016ZC0062) and Medical Scientific Research Foundation of Guangdong Province, China (A2015153).

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Authors and Affiliations

  1. Department of Neurology, The Third Affiliated Hospital of Southern Medical University, No. 183, Zhongshan Road West, Guangzhou, Guangdong, 510630, China

    Qinggan Zeng, Yifeng Luo, Bingxun Lu & Xiaofeng Wang

  2. Department of Neurology, The First People’s Hospital of Huaihua, Affiliated to University of South China, No. 144, Jinxi Road South, Huaihua, 418000, China

    Rongyong Man, Ling Zeng & Yushi Zhong

Authors
  1. Qinggan Zeng
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  2. Rongyong Man
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  3. Yifeng Luo
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  4. Ling Zeng
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  5. Yushi Zhong
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  6. Bingxun Lu
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  7. Xiaofeng Wang
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Corresponding author

Correspondence to Xiaofeng Wang.

Additional information

Qinggan Zeng, Rongyong Man, and Yifeng Luo are co-first authors.

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Zeng, Q., Man, R., Luo, Y. et al. IRF-8 is Involved in Amyloid-β1–40 (Aβ1–40)-induced Microglial Activation: a New Implication in Alzheimer’s Disease. J Mol Neurosci 63, 159–164 (2017). https://doi.org/10.1007/s12031-017-0966-1

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  • DOI: https://doi.org/10.1007/s12031-017-0966-1

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