title: Effects of pro-inflammatory cytokines on cannabinoid CB1 and CB2 receptors in immune cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The levels of CB1 and CB2 can be upregulated by inflammatory cytokines, which can explain their increase in inflammatory conditions including MS.
authors.affiliation: Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: L
authors.initials: L
authors.lastname: Jean-Gilles
authors.forename: M
authors.initials: M
authors.lastname: Braitch
authors.forename: M L
authors.initials: ML
authors.lastname: Latif
authors.forename: J
authors.initials: J
authors.lastname: Aram
authors.forename: A J
authors.initials: AJ
authors.lastname: Fahey
authors.forename: L J
authors.initials: LJ
authors.lastname: Edwards
authors.forename: R A
authors.initials: RA
authors.lastname: Robins
authors.forename: R
authors.initials: R
authors.lastname: Tanasescu
authors.forename: P J
authors.initials: PJ
authors.lastname: Tighe
authors.forename: B
authors.initials: B
authors.lastname: Gran
authors.forename: L C
authors.initials: LC
authors.lastname: Showe
authors.forename: S P
authors.initials: SP
authors.lastname: Alexander
authors.forename: V
authors.initials: V
authors.lastname: Chapman
authors.forename: D A
authors.initials: DA
authors.lastname: Kendall
authors.forename: C S
authors.initials: CS
authors.lastname: Constantinescu
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D014409:Tumor Necrosis Factor-alpha
keywords: cannabinoid receptor 1; cannabinoid receptor 2; inflammatory cytokines; multiple sclerosis; regulation