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

## TL;DR

Nicotine reduces inflammation in microglia cells and protects neurons by activating a specific receptor, potentially offering new therapeutic approaches.

## Contribution

This study reveals nicotine's anti-inflammatory and neuroprotective effects via α7 nAChR activation in microglia.

## Key findings

- Nicotine inhibits LPS-induced inflammation in HMC3 microglia.
- Nicotine promotes neurotrophic factor release and neuronal survival through α7 nAChR activation.
- The anti-inflammatory effects involve increased PI3K phosphorylation.

## 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.