Interferon Regulatory Factor 5 Mediates Lipopolysaccharide-Induced Neuroinflammation.

Ziqi Fan, Shuai Zhao, Yueli Zhu, Zheyu Li, Zhirong Liu, Yaping Yan, Jun Tian, Yanxing Chen, Baorong Zhang

Frontiers in immunology 2020

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Activated microglia play a vital role in neuroinflammation in the central nervous system (CNS), which is associated with the pathogenesis and the progression of neurological diseases. Interferon regulatory factor 5 (IRF5) has been well established participating in inflammatory responses and is highly expressed in M1 macrophage in the periphery, the role of which in the CNS remains elusive. Lipopolysaccharide (LPS) was employed to induce neuroinflammation. Down-regulation of IRF5 in C57/BL6 mice and BV2 microglial cells were achieved by IRF5 siRNA transfection. The levels of pro-inflammatory cytokines were evaluated by ELISA and quantitative real-time PCR. The expression levels of IRF5 were examined by immunofluorescence and Western blot. LPS induced significantly elevated expression of IRF5 in mouse brain, which co-localized with CD11b-positive microglia. Down-regulation of IRF5 quenched the pro-inflammatory responses. The levels of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were up-regulated at 4 h after LPS treatment, which were significantly down-regulated with the knockdown of IRF5. LPS-induced pro-inflammatory responses were transient, which were comparable to control group at 24 h after LPS treatment. However, LPS did not up-regulate the expression of IRF5 in BV2 microglial cells, indicating that LPS-induced inflammation in BV2 cells does not involve IRF5 signaling. IRF5 mediates the inflammatory responses in the CNS, which might serve as a therapeutic target for CNS inflammatory diseases. LPS-induced inflammation does not involve IRF5 signaling in BV2 microglia. Copyright © 2020 Fan, Zhao, Zhu, Li, Liu, Yan, Tian, Chen and Zhang.

Citation

Ziqi Fan, Shuai Zhao, Yueli Zhu, Zheyu Li, Zhirong Liu, Yaping Yan, Jun Tian, Yanxing Chen, Baorong Zhang. Interferon Regulatory Factor 5 Mediates Lipopolysaccharide-Induced Neuroinflammation. Frontiers in immunology. 2020;11:600479