JWH133 inhibits MPP+-induced inflammatory response and iron influx in astrocytes

Neurosci Lett. 2020 Feb 16:720:134779. doi: 10.1016/j.neulet.2020.134779. Epub 2020 Jan 22.

Abstract

Background: We investigated the anti- inflammatory effect of type II cannabinoid receptor (CB2 receptor) activation and their relationship to iron influx on 1-methyl-4-phenylpyridinium (MPP+) treated astrocytes.

Methods and results: By western blots, real-time PCR and ELISA, the expressions of CB2 receptor, divalent metal transporter-1 (DMT1), cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), interleukin-1β (IL-1β) and tumor necrosis factor- α (TNF-α) were measured. Iron influx into astrocytes was determined by the quenching of calcein fluorescence. We found that pre-treatment with JWH133, a selective CB2 receptor agonist, significantly suppressed the MPP+-induced up-regulation of COX-2, iNOS, IL- 1β and TNF-α in astrocytes. In addition, JWH133 significantly inhibited the MPP+-induced up- regulation of DMT1. Further studies indicated that JWH133 suppressed the MPP+-accelerated iron influx into astrocytes. These effects were blocked by co-treatment with AM630, the CB2 receptor antagonist.

Conclusions: These results suggest that activation of CB2 receptor inhibit MPP +-induced inflammatory response and iron influx in astrocytes.

Keywords: Anti-Inflammatory; Astrocyte; Divalent metal transporter-1; Iron; Type II cannabinoid receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / administration & dosage*
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Astrocytes / drug effects*
  • Astrocytes / metabolism*
  • Cannabinoids / administration & dosage*
  • Cells, Cultured
  • Encephalitis / metabolism*
  • Encephalitis / prevention & control
  • Iron / metabolism*
  • Mesencephalon / drug effects
  • Mesencephalon / metabolism
  • Rats
  • Receptor, Cannabinoid, CB2 / metabolism*
  • Up-Regulation

Substances

  • Anti-Inflammatory Agents
  • Cannabinoids
  • Cnr2 protein, rat
  • Receptor, Cannabinoid, CB2
  • Iron
  • 1-Methyl-4-phenylpyridinium
  • 1,1-dimethylbutyl-1-deoxy-Delta(9)-THC