A novel tri‐culture model for neuroinflammation

Yan‐Fang Zheng, Xian Zhou, Dennis Chang, Deep Jyoti Bhuyan, Jie Ping Zhang, Wen‐Zhen Yu, Xia‐Sen Jiang, Sai Wang Seto, Seung Yeon Yeon, Jia Li, Chun Guang Li

Research output: Contribution to journalArticle

Abstract

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. (Figure presented.).

Original languageEnglish
Pages (from-to)249-261
Number of pages13
JournalJournal of Neurochemistry
Volume156
Issue number2
Early online date5 Sep 2020
DOIs
Publication statusPublished - Jan 2021

Keywords

  • destructed endothelial barrier
  • microglia activation
  • neuroinflammation
  • neuron injury
  • tri-culture

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