Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells

Jean-Gilles, L.; Braitch, M.; Latif, M. L.; Aram, J.; Fahey, A. J.; Edwards, L. J.; Robins, R. A.; Tanasescu, R.; Tighe, P. J.; Gran, B.; Showe, L. C.; Alexander, S. P.; Chapman, V.; Kendall, D. A.; Constantinescu, C. S.

Abstract

© 2015 The Authors. Aims: To investigate the regulation of cannabinoid receptors CB1 and CB2 on immune cells by pro-inflammatory cytokines and its potential relevance to the inflammatory neurological disease, multiple sclerosis (MS). CB1 and CB2 signalling may be anti-inflammatory and neuroprotective in neuroinflammatory diseases. Cannabinoids can suppress inflammatory cytokines but the effects of these cytokines on CB1 and CB2 expression and function are unknown. Methods: Immune cells from peripheral blood were obtained from healthy volunteers and patients with MS. Expression of CB1 and CB2 mRNA in whole blood cells, peripheral blood mononuclear cells (PBMC) and T cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Expression of CB1 and CB2 protein was determined by flow cytometry. CB1 and CB2 signalling in PBMC was determined by Western blotting for Erk1/2. Results: Pro-inflammatory cytokines IL-1β, IL-6 and TNF-α (the latter likely NF-κB dependently) can upregulate CB1 and CB2 on human whole blood and peripheral blood mononuclear cells (PBMC). We also demonstrate upregulation of CB1 and CB2 and increased IL-1β, IL-6 and TNF-α mRNA in blood of patients with MS compared with controls. Conclusion: The levels of CB1 and CB2 can be upregulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS.

Citation

Jean-Gilles, L., Braitch, M., Latif, M. L., Aram, J., Fahey, A. J., Edwards, L. J., …Constantinescu, C. S. (2015). Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells. Acta Physiologica, 214(1), 63-74. https://doi.org/10.1111/apha.12474

• Journal Article Type: Article
• Acceptance Date: Feb 16, 2015
• Online Publication Date: Mar 10, 2015
• Publication Date: May 1, 2015
• Deposit Date: Nov 12, 2019
• Publicly Available Date: Nov 14, 2019
• Journal: Acta Physiologica
• Print ISSN: 1748-1708
• Electronic ISSN: 1748-1716
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 214
• Issue: 1
• Pages: 63-74
• DOI: https://doi.org/10.1111/apha.12474
• Public URL: https://nottingham-repository.worktribe.com/output/3096226
• Publisher URL: https://onlinelibrary.wiley.com/doi/full/10.1111/apha.12474
• Contract Date: Nov 14, 2019