2. Academic Validation
  3. Nicotine Regulates LPS-Induced Inflammatory Responses in HMC3 Microglia and Exerts Neuronal Protection

Nicotine Regulates LPS-Induced Inflammatory Responses in HMC3 Microglia and Exerts Neuronal Protection

  • Mediators Inflamm. 2026 Jan 21:2026:4652344. doi: 10.1155/mi/4652344.
Yuhan Qin 1 2,  Xiaohui Yan 1 2,  Yanbo Luo 2,  Hongjuan Wang 1 2,  Yushan Tian 1 2,  Xiaqing Wu 1 2,  Huan Chen 1 2,  Hongwei Hou 1 2 3,  Qingyuan Hu 1 2
Affiliations

Affiliations

  • 1 Beijing Life Science Academy, Beijing, 102209, China.
  • 2 Key Laboratory of Tobacco Biological Effects, China National Tobacco Quality Supervision and Test Center, No. 6 Cuizhu Street, New & High-tech Industry Development Zone, Zhengzhou, 450001, China.
  • 3 Department of Chemistry, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University, Beijing, 100084, China, tsinghua.edu.cn.
PMID: 41583120 DOI: 10.1155/mi/4652344
Abstract

Microglia-mediated neuroimmune responses have been implicated in central nervous system injury and disease pathogenesis. The α7 nicotinic acetylcholine receptor (α7 nAChR), which is expressed on microglia and participates in microenvironment interactions, is a key mediator of the cholinergic anti-inflammatory pathway. Nicotine activates the α7 nAChR, which may mediate the inflammation of microglia. This study aims to explore the modulatory effects of nicotine on neuroinflammation and its potential indirect neuroprotective effects using an in vitro microglial cell inflammation model. In our study, inflammatory phenotype indicators and molecular mechanisms of HMC3 cells were analyzed. Furthermore, an HMC3 microglia-SH-SY5Y neuronal coculture system was constructed to investigate the indirect neuroprotective effects of nicotine. The results demonstrated that nicotine exerted an inhibitory effect on the lipopolysaccharide-induced HMC3 microglia inflammation, promoted the release of Neurotrophic Factors, and neuronal survival by altering the immune environment. These effects appear to be mediated through the activation of α7 nAChR, leading to an increase in phosphorylation of PI3K. This study provides important insights into the immunomodulatory functions of low-concentration nicotine in the nervous system and contributes to a deeper understanding of its potential therapeutic applications.

Keywords

HMC3; PI3K; cell coculture; lipopolysaccharide; microglia; neurodegenerative disease; neuroinflammation; neuron; nicotine; α7 nAChR.

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