A novel tri‐culture model for neuroinflammation

A novel tri‐culture model for neuroinflammation.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1111/jnc.15171
Journal or Publication Title: Journal of Neurochemistry
Date: 2020
Divisions: Vascular Biology
Depositing User: General Admin
Identification Number: 10.1111/jnc.15171
ISSN: 0022-3042
Date Deposited: 03 Jan 2021 23:49

Neuroinflammation is believed to play a primary role in the pathogenesis of most neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and schizophrenia. Currently, suitable in vitro neuroinflammation models for studying cellular interactions and inflammatory mechanisms at the neurovascular unit are still scarce. In this study, we established an experimentally flexible tri‐culture neuroinflammation model combining murine microglial cells (N11), mouse neuroblastoma Nuro2A cell lines and brain microvascular endothelial MVEC(B3) cells in a transwell co‐culture system stimulated with lipopolysaccharides. Neuroinflammation was induced in this tri‐culture model as manifested by activated N11 cells via toll‐like receptor 4, resulting in increased release of proinflammatory mediators (nitric oxide, interleukin‐6 and tumour necrosis factor‐α) through the activation of nuclear factor‐κB signalling pathway. The released inflammatory cytokines from N11 in turn, damaged the tight junction in microvascular endothelial MVEC(B3) cells, increased permeability of endothelial barrier, and induced tau phosphorylation and up‐regulated caspase‐3 expression in mouse neuroblastoma Nuro2A cell lines, leading to neuroinflammation injury. In summary, this tri‐culture inflammation model mimics the microenvironment, the cellular crosstalk and the molecular events that take place during neuroinflammation. It provides a robust in vitro model for studying neuroinflammation mechanisms and screening for potential therapeutics to treat various neurodegenerative diseases.

Zheng, Yan‐Fang
Zhou, Xian
Chang, Dennis
Bhuyan, Deep Jyoti
Zhang, Jie Ping
Yu, Wen‐Zhen
Jiang, Xia‐Sen
Seto, Sai Wang
Yeon, Seung Yeon
Li, Jia
Li, Chun Guang
Last Modified: 03 Jan 2021 23:49
URI: https://eprints.centenary.org.au/id/eprint/839

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