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

Acta Physiologica - Tập 214 Số 1 - Trang 63-74 - 2015
Lucie Jean-Gilles1, Manjit Braitch1, M.L. Latif2, Jehan Aram1, A. J. Fahey1, Laura Edwards1, R. A. Robins3, Radu Tănăsescu4,1, Patrick J. Tighe3, Bruno Gran1, Louise C. Showe5, S P H Alexander2, Victoria Chapman2, Dave Kendal2, Cris S. Constantinescu1
1Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK
2Division of Neuroscience, School of Life Sciences, University of Nottingham, Nottingham, UK
3Division of Immunity, School of Life Sciences, University of Nottingham, Nottingham, UK
4Department of Neurology, Colentina Hospital, University of Medicine and Pharmacy Carol Davila, Bucharest, Romania
5The Wistar Institute, Philadelphia, PA, USA

Tóm tắt

AbstractAims

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 (qRTPCR). 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 TNFα (the latter likely NFκB 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 TNFα 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.

Từ khóa


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