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The role of ZC3H12D-regulated TLR4-NF-κB pathway in LPS-induced pro-inflammatory microglial activation

Jinyun Long1, Xiukuan Li1, Chunyan Yao2

  • 1School of Public Health, the key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 561113, China; Department of Epidemiology, College of Preventive Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University (Third Military Medical University), Chongqing 400038, China.

Neuroscience Letters
|May 2, 2024
PubMed

Insights

Lipopolysaccharide (LPS) triggers neuroinflammation by activating microglia. This study reveals ZC3H12D inhibits this activation by targeting the TLR4-NF-κB pathway, offering therapeutic potential for neuroinflammation.

Area of Science:

  • Neuroscience
  • Immunology
  • Molecular Biology

Background:

  • Lipopolysaccharide (LPS) is a potent neurotoxin known to induce microglial activation and neuroinflammation.
  • ZC3H12D is an emerging immunomodulator with potential roles in neurological conditions, but its specific involvement in microglial activation remained uncharacterized.

Purpose of the Study:

  • To investigate the role of ZC3H12D in regulating lipopolysaccharide (LPS)-induced pro-inflammatory microglial activation.
  • To elucidate the underlying molecular mechanisms by which ZC3H12D influences microglial responses to LPS.

Main Methods:

  • Establishment of animal models using intraperitoneal LPS injection to assess motor function and cerebral microglial activation.
  • In vitro studies using BV-2 microglia treated with LPS to analyze ZC3H12D expression and its impact on inflammatory pathways.
  • Investigation of the Toll-like receptor 4 (TLR4)-nuclear factor-kappa B (NF-κB) signaling pathway and the effect of ZC3H12D and resveratrol.

Main Results:

  • LPS administration impaired motor function and induced pro-inflammatory microglial activation in mice, accompanied by decreased ZC3H12D expression.
  • In vitro, reduced ZC3H12D expression correlated with LPS-induced microglial activation; enhancing ZC3H12D expression inhibited this activation.
  • LPS-induced activation of the TLR4-NF-κB pathway was reversed by promoting ZC3H12D expression, an effect also observed with resveratrol.

Conclusions:

  • ZC3H12D plays a critical role in suppressing LPS-induced pro-inflammatory activation of microglia in the brain.
  • ZC3H12D exerts its neuroprotective effects by inhibiting the TLR4-NF-κB signaling pathway.
  • ZC3H12D represents a potential therapeutic target for mitigating neuroinflammation and related neurological injuries.
Keywords:
InflammationLPSMicrogliaTLR4-NF-κB pathwayZC3H12D

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