학술논문
Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells.
Document Type
Academic Journal
Author
Jean-Gilles L; Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK.; Braitch M; Latif ML; Aram J; Fahey AJ; Edwards LJ; Robins RA; Tanasescu R; Tighe PJ; Gran B; Showe LC; Alexander SP; Chapman V; Kendall DA; Constantinescu CS
Source
Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101262545 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1748-1716 (Electronic) Linking ISSN: 17481708 NLM ISO Abbreviation: Acta Physiol (Oxf) Subsets: MEDLINE
Subject
Language
English
Abstract
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.
(© 2015 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)
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.
(© 2015 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)