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Cytokine. 2019 Jul;119:113-118. doi: 10.1016/j.cyto.2019.03.003. Epub 2019 Mar 21.

IL-18 induced IL-23/IL-17 expression impairs Aβ clearance in cultured THP-1 and BV2 cells.

Author information

1
Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, 197 Ruijin No. 2 Road, Shanghai 200025, China; Department of Neurology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Discipline Construction Research Center of China Hospital Development Institute, Shanghai Jiao Tong University, 280 Mohe Road, Shanghai 201999, China.
2
Department of Psychiatry, Tongji Hospital, Tongji University School of Medicine, 389 Xin Cun Road, Shanghai 200065, China; Shanghai Mental Health Central, Shanghai Jiao Tong University School of Medicine, 600 Wanping Nan Road, Shanghai 200013, China.
3
Department of Learning, Informatics, Management and Ethics, Karolinska Institute, Stockholm 17177, Sweden.
4
Department of Neurology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Discipline Construction Research Center of China Hospital Development Institute, Shanghai Jiao Tong University, 280 Mohe Road, Shanghai 201999, China.
5
Department of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, 197 Ruijin No. 2 Road, Shanghai 200025, China. Electronic address: qicheng@shsmu.edu.cn.

Abstract

Recent studies have provided overwhelming evidence of the involvement of microglia-related molecular networks in the pathogenesis of Alzheimer's diseases (AD). The potential involvement of pro-inflammatory cytokines interleukin (IL)-18, IL-23 and IL-17 on amyloid (Aβ) clearance is still unclear. In this study, we addressed that there might be a net relationship among IL-18, IL-23, and IL-17 and they can affect Aβ clearance in cultured macrophage/microglia cells. In human macrophage cell line THP-1, Aβ42 incubation could increase the expression of IL-18, IL-23 and IL-17 in a concentration dependent manner. THP-1 cell could clear Aβ42 in the culture medium time-dependently, but its capacity of Aβ clearance was impaired by IL-18, IL-23 or IL-17 treatment. Similarly, the capacity of the microglia cell line BV2 to clear Aβ42 was impaired by IL-18, IL-23 or IL-17 treatment. In co-cultures of BV2 with APP/PS1 neuron, Aβ was efficiently cleared by BV2 cell, but Aβ clearance was impaired by IL-18, IL-23 or IL-17 treatment. The effects of IL-18, IL-23 and IL-17 could be blocked by their corresponding neutralizing antibodies. In addition, the inhibitory effects of IL-18 were blocked by IL-23 or IL-17 neutralizing antibodies while the inhibitory effects of IL-23 were blocked by IL-17 neutralizing antibodies. Our study provides evidences showing that amyloid induced IL-18/IL-23/IL-17 axis could impair macrophage and microglia-mediated Aβ clearance. Thus, IL-18/IL-23/IL-17 axis might be a therapeutic target in AD.

KEYWORDS:

Alzheimer’s disease; Amyloid; Cytokines; Inflammation; Interleukin

PMID:
30903865
DOI:
10.1016/j.cyto.2019.03.003

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