Microglial C/EBPβ-Fcgr1 regulatory axis blocking inhibits microglial pyroptosis and improves neurological recovery.

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. © 2025. The Author(s).

Citation

Jing Li, Yubing Yang, Chenguang Zhao, Jinghao Zhao, Xiaohui Wang, Shengshou Ye, Dong Wang, Chengdong Zhou, Jie Li, Shuang Wang, Ke Li, Chunmiao Liu, Xijing He, Jie Qin. Microglial C/EBPβ-Fcgr1 regulatory axis blocking inhibits microglial pyroptosis and improves neurological recovery. Journal of neuroinflammation. 2025 Jan 31;22(1):29

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PMID: 39891259

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