Author(s): Hassan S, Eldeeb K, Millns PJ, Bennett AJ, Alexander SP,
Abstract Share this page
Abstract BACKGROUND AND PURPOSE: Microglial cells are important mediators of the immune response in the CNS. The phytocannabinoid, cannabidiol (CBD), has been shown to have central anti-inflammatory properties, and the purpose of the present study was to investigate the effects of CBD and other phytocannabinoids on microglial phagocytosis. EXPERIMENTAL APPROACH: Phagocytosis was assessed by measuring ingestion of fluorescently labelled latex beads by cultured microglial cells. Drug effects were probed using single-cell Ca²⁺ imaging and expression of mediator proteins by immunoblotting and immunocytochemistry. KEY RESULTS: CBD (10 μM) enhanced bead phagocytosis to 175 ± 7\% control. Other phytocannabinoids, synthetic and endogenous cannabinoids were without effect. The enhancement was dependent upon Ca²⁺ influx and was abolished in the presence of EGTA, the Ca²⁺ channel inhibitor SKF96365, the transient receptor potential (TRP) channel blocker ruthenium red, and the TRPV1 antagonists capsazepine and AMG9810. CBD produced a sustained increase in intracellular Ca²⁺ concentration in BV-2 microglia and this was abolished by ruthenium red. CBD rapidly increased the expression of TRPV2 and TRPV1 proteins and caused a translocation of TRPV2 to the cell membrane. Wortmannin blocked CBD enhancement of BV-2 cell phagocytosis, suggesting that it is mediated by PI3K signalling downstream of the Ca²⁺ influx. CONCLUSIONS AND IMPLICATIONS: The TRPV-dependent phagocytosis-enhancing effect of CBD suggests that pharmacological modification of TRPV channel activity could be a rational approach to treating neuroinflammatory disorders involving changes in microglial function and that CBD is a potential starting point for future development of novel therapeutics acting on the TRPV receptor family. © 2014 The British Pharmacological Society.
This article was published in Br J Pharmacol
and referenced in Pharmaceutica Analytica Acta