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Neuroinflammatory and Amyloidogenic Activities of IL-32β in Alzheimer’s Disease

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Abstract

Interleukin (IL)-32β can act as either pro-inflammatory or anti-inflammatory cytokines with being dependent on the status of disease development. Herein, we investigated whether IL-32β overexpression changes cytokine levels and affects amyloid-beta (Aβ)-induced pro-inflammation in the brain. IL-32β transgenic (Tg) mice and non-Tg mice were intracerebroventricularly infused with Aβ1-42 once a day for 14 days, and then cognitive function was assessed by the Morris water maze test and passive avoidance test. Our data showed that IL-32β Tg mice increased memory impairment, glia activation, amyloidogenesis, and neuroinflammation. The expression of glial fibrillary acid protein (GFAP), Iba1, and β-secretase 1 (BACE1) in the cortex and hippocampus was much higher in the Aβ1-42-infused IL-32β Tg mice brain. The activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor-kappa B (NF-κB) was much higher in Aβ1-42-infused IL-32β Tg mice brain. We also found that cytokines including IP-10, GM-CSF, JE, IL-13, and interferone-inducible T cell α chemoattractant (I-TAC) were elevated in Aβ1-42-infused IL-32β Tg mice brain. These results suggest that IL-32β could activate NF-κB and STAT3, and thus affect neuroinflammation as well as amyloidogenesis, leading to worsening memory impairment.

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Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MISP) (No. MRC, 2008-0062275), by a grant (A101836) from the Korean Health Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea.

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Authors and Affiliations

  1. College of Pharmacy, Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, South Korea

    Hyung-Mun Yun, Jin A. Kim, Chul Ju Hwang, Peng Jin, Myung Ki Baek, Jin Moo Lee, Ji Eun Hong, Sang Min Lee, Sang Bae Han, Ki Wan Oh & Jin Tae Hong

  2. College of Pharmacy, Yeungnam University, 280 Daehak-Ro, Gyeongsan, Gyeongbuk, 712-749, South Korea

    Dong Young Choi

  3. Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, 143-701, South Korea

    Do Young Yoon

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  1. Hyung-Mun Yun
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  2. Jin A. Kim
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Correspondence to Jin Tae Hong.

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Jin A. Kim contributed equally to this work.

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Yun, HM., Kim, J.A., Hwang, C.J. et al. Neuroinflammatory and Amyloidogenic Activities of IL-32β in Alzheimer’s Disease. Mol Neurobiol 52, 341–352 (2015). https://doi.org/10.1007/s12035-014-8860-0

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