Abstract
BackgroundActivated 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.MethodsLipopolysaccharide (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.ResultsLPS 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.ConclusionsIRF5 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.
Highlights
Microglia play a central role in the immune surveillance of the central nervous system (CNS), which is activated under pathological conditions to maintain the homeostasis of CNS [1]
We initially intended to investigate the role of Interferon regulatory factor 5 (IRF5) in vitro with BV2 microglial cells
We demonstrated that like in the periphery, IRF5 plays an essential role in the activation of microglia in the CNS
Summary
Microglia play a central role in the immune surveillance of the central nervous system (CNS), which is activated under pathological conditions to maintain the homeostasis of CNS [1]. IRF5 is a crucial regulator of the cell cycle, apoptosis, and inflammation in the peripheral It is required for the expression of TLR (TLR4/7/8/9) mediated pro-inflammatory cytokines like TNF, IL-6, IL-12, and so on [4, 11]. A recent study found that the expression of IRF5 influenced stroke outcomes [12], which was related to IRF5 mediated activation of microglia and regulation of neuroinflammation. 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
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