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.

Neuroreport
|November 9, 2020
PubMed
Abstract

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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