FKBP5 promotes pro-inflammatory microglial activation and neuronal injury through NF-κB/NLRP3 signaling in convulsive status epilepticus.

Authors

Haiping Zhang, Lin Wu, Ting Su, Mei Yuan

Published in

Immunopharmacology and immunotoxicology. Pages 1-15. Sep 08, 2026. Epub Sep 08, 2026.

Abstract

Convulsive status epilepticus (CSE) triggers profound neuroinflammatory responses that exacerbate neuronal injury and impair long-term neurological recovery. FKBP5, a co-chaperone protein implicated in immune regulation, has been increasingly recognized as a modulator of inflammatory signaling. However, its role in microglial activation and neuroinflammation during CSE remains elusive.
A pilocarpine-induced mouse model of CSE was established to investigate FKBP5 expression dynamics in microglia. FKBP5 was silenced in vitro by siRNA transfection in primary microglia isolated from CSE model mice. Subsequently, microglia were co-cultured with primary cortical neurons to evaluate the impact of FKBP5-regulated microglial activation on neuronal survival and inflammatory response. Western blotting, immunofluorescence, and quantitative PCR were used to assess microglial activation phenotype markers, NF-κB activation, and NLRP3 inflammasome-related priming.
FKBP5 expression was markedly upregulated in microglia following CSE, correlating with an enhanced pro-inflammatory phenotype and increased pro-inflammatory cytokine production. FKBP5 knockdown suppressed NF-κB activation, reduced NF-κB p65 nuclear translocation, and decreased NLRP3 inflammasome-related protein expression. In primary microglia, FKBP5 knockdown attenuated CSE-associated pro-inflammatory activation and decreased secretion of IL-1β and TNF-α. In microglia-neuron co-culture, FKBP5 knockdown reduced neuronal apoptosis and inflammatory injury, suggesting an indirect role of FKBP5 in modulating neuroinflammation and neuronal damage in the CSE context.
Our study identifies FKBP5 as an upstream modulator of NF-κB/NLRP3 signaling in microglia during convulsive status epilepticus. Targeting FKBP5 may represent a promising strategy to ameliorate neuroinflammation and neuronal injury in epilepsy.

PMID:
42707019
Bibliographic data and abstract were imported from PubMed on 08 Sep 2026.

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