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

Abstract

BackgroundWe 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 ResultsBy 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. ConclusionsThese results suggest that activation of CB2 receptor inhibit MPP +-induced inflammatory response and iron influx in astrocytes.