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Updated: May 29, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglial C/EBPβ-Fcgr1 regulatory axis blocking inhibits microglial pyroptosis and improves neurological recovery
Jing Li1, Yubing Yang1, Chenguang Zhao2
1Department of Orthopedics, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Abstract:
CAAT/Enhancer Binding Protein β (C/EBPβ) is associated with inflammatory responses in neurodegenerative pathologies, particularly in the brain. However, the regulatory role of C/EBPβ in spinal cord injury and its impact on neurological recovery remain unknown. In this study, we observed significant upregulation of C/EBPβ in microglia after spinal cord injury in mice and was associated with neuroinflammation. Knocking down C/EBPβ in the spinal cord attenuated microglia pyroptosis, reduced the production of proinflammatory cytokines, and inhibited neuronal apoptosis. Mechanistically, C/EBPβ promoted the transcription of Fcgr1, which was involved in activating microglia pyroptosis. In both in-vivo and in-vitro experiments, knocking down Cebpb or Fcgr1, or the pyroptosis inhibitor VX765 inhibited neuronal apoptosis and improved neurological recovery in mice. These findings indicate that C/EBPβ functions as a key regulator that participates in the microglia pyroptosis-mediated neuroinflammation by activating Fcgr1 transcription.
Insights
CAAT/Enhancer Binding Protein β (C/EBPβ) drives neuroinflammation after spinal cord injury by activating microglia pyroptosis via Fcgr1. Inhibiting C/EBPβ or Fcgr1 improves neurological recovery.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- CAAT/Enhancer Binding Protein β (C/EBPβ) is implicated in neuroinflammation in neurodegenerative diseases.
- The specific role of C/EBPβ in spinal cord injury (SCI) and neurological recovery is not well understood.
Purpose of the Study:
- To investigate the regulatory role of C/EBPβ in SCI-induced neuroinflammation and its impact on neurological recovery.
- To elucidate the underlying molecular mechanisms involving C/EBPβ in SCI.
Main Methods:
- Assessed C/EBPβ expression in microglia following SCI in a mouse model.
- Utilized knockdown of C/EBPβ (Cebpb) and Fcgr1 in vivo and in vitro.
- Measured microglia pyroptosis, pro-inflammatory cytokine production, and neuronal apoptosis.
- Investigated the transcriptional regulation of Fcgr1 by C/EBPβ.
- Administered pyroptosis inhibitor VX765.
Main Results:
- C/EBPβ was significantly upregulated in microglia post-SCI, correlating with neuroinflammation.
- Knockdown of C/EBPβ reduced microglia pyroptosis, pro-inflammatory cytokine release, and neuronal apoptosis.
- C/EBPβ was found to promote Fcgr1 transcription, which mediates microglia pyroptosis.
- Inhibition of Cebpb or Fcgr1, or VX765 treatment, attenuated neuronal apoptosis and improved neurological outcomes in mice.
Conclusions:
- C/EBPβ acts as a critical regulator in SCI-induced neuroinflammation.
- C/EBPβ exacerbates SCI by promoting microglia pyroptosis through Fcgr1 activation.
- Targeting C/EBPβ or Fcgr1 presents a potential therapeutic strategy for improving neurological recovery after spinal cord injury.
