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Downregulation of Gbp2 Attenuates LPS-Induced Inflammation in BV2 Microglia Cells Through Inhibition of STAT1

Yang Bao1,2, Hongwei Ni1,2, Kai Wang1

  • 1Department of Anesthesiology, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Shanghai, 201800, People's Republic of China.

Journal of Inflammation Research
|October 13, 2025
PubMed
Abstract

Insights

Postoperative cognitive dysfunction (POCD) is linked to neuroinflammation. This study found Gbp2 is highly expressed in POCD patients and its downregulation reduces inflammation and cell death, suggesting new therapeutic targets.

Area of Science:

  • Neuroscience
  • Immunology
  • Molecular Biology

Background:

  • Postoperative cognitive dysfunction (POCD) affects approximately 50% of patients within weeks of surgery.
  • Microglial activation and neuroinflammation are key contributors to POCD.
  • Identifying molecular mechanisms underlying POCD is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the role of inflammation-associated genes in POCD.
  • To identify potential therapeutic targets for mitigating POCD-related neuroinflammation and cognitive decline.

Main Methods:

  • Screening of inflammation-associated differentially expressed genes (DEGs) using GEO databases.
  • Quantitative PCR and Western blot for mRNA and protein expression analysis.
  • ELISA for measuring IL-6 and TNF-α concentrations.

Main Results:

  • Guanine nucleotide-binding protein (Gbp2) was significantly upregulated in POCD patient samples and associated with inflammatory responses.
  • Knockdown of Gbp2 reversed lipopolysaccharide (LPS)-induced inflammation and apoptosis in mouse microglial BV2 cells.
  • Gbp2 deficiency exerted anti-apoptotic and anti-inflammatory effects mediated by STAT1 and Irf1.

Conclusions:

  • Gbp2 is highly expressed in patients with POCD compared to non-POCD patients post-surgery.
  • Downregulation of Gbp2 attenuates LPS-induced inflammation by inhibiting STAT1.
  • Targeting Gbp2 may offer a novel therapeutic strategy for preventing or treating POCD.
Keywords:
Gbp2STAT1neuroinflammationpostoperative cognitive dysfunction

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