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Updated: Dec 1, 2025

Live Imaging of Nicotine Induced Calcium Signaling and Neurotransmitter Release Along Ventral Hippocampal Axons
Published on: June 24, 2015
Nicotine induces P2X4 receptor, interleukin-1 beta, and brain-derived neurotrophic factor expression in BV2 microglia
Lina Guo1,2, Yang Zhang2, Qing Lv2
1Department of Anesthesiology, Cheeloo College of Medicine, Shandong University.
Objective:
Upregulation of P2X4 receptor (P2X4R), brain-derived neurotrophic factor (BDNF), and interleukin-1 beta (IL-1β) in activated microglia is associated with hyperalgesia. This study investigated whether nicotine increases pain hypersensitivity by altering the expression of these molecules in microglia. We also examined the role of interferon regulatory factor 8 (IRF8) in this process.
Methods:
Experiments were performed in BV2 microglial cells. IRF8 was knocked down or overexpressed using lentiviruses harboring a short hairpin RNA targeting IRF8 or an IRF8 overexpression construct, respectively. P2X4R, BDNF, and IL-1β mRNA and protein levels were evaluated by real-time PCR and western blotting, respectively, and BDNF and IL-1β secretion was assessed by ELISA.
Results:
Chronic nicotine exposure enhanced the expression of P2X4R, BDNF, and IL-1β in BV2 cells, and stimulated the release of BDNF and IL-1β in the presence of ATP. IRF8 was found to mediate the nicotine-induced increases in BDNF and IL-1β mRNA and P2X4R protein levels in BV2 cells.
Conclusion:
Nicotine may increase pain hypersensitivity by promoting the expression of P2X4R, BDNF, and IL-1β through modulation of IRF8 levels in microglial cells.
Insights
Nicotine exposure increases pain hypersensitivity by upregulating microglial P2X4 receptor (P2X4R), brain-derived neurotrophic factor (BDNF), and interleukin-1 beta (IL-1β). Interferon regulatory factor 8 (IRF8) mediates these nicotine-induced changes.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Activated microglia express P2X4 receptor (P2X4R), brain-derived neurotrophic factor (BDNF), and interleukin-1 beta (IL-1β), contributing to hyperalgesia.
- Nicotine's role in pain hypersensitivity is linked to microglial activation and inflammatory mediators.
Purpose of the Study:
- Investigate nicotine's effect on P2X4R, BDNF, and IL-1β expression in microglia.
- Determine the role of interferon regulatory factor 8 (IRF8) in nicotine-induced pain hypersensitivity.
Main Methods:
- Utilized BV2 microglial cells for experiments.
- Manipulated IRF8 levels via knockdown and overexpression using lentiviral vectors.
- Quantified gene and protein expression of P2X4R, BDNF, and IL-1β using real-time PCR and western blotting.
- Measured BDNF and IL-1β secretion via ELISA.
Main Results:
- Chronic nicotine exposure significantly enhanced P2X4R, BDNF, and IL-1β expression in BV2 cells.
- Nicotine stimulated BDNF and IL-1β release in the presence of ATP.
- IRF8 was identified as a key mediator of nicotine-induced increases in BDNF, IL-1β mRNA, and P2X4R protein.
Conclusions:
- Nicotine may exacerbate pain hypersensitivity through IRF8-mediated modulation of microglial P2X4R, BDNF, and IL-1β.
- IRF8 plays a critical role in the neuroinflammatory pathways underlying nicotine-induced hyperalgesia.
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