Effect of the cannabinoid receptor ligand, WIN 55,212-2, on superoxide anion and TNF-alpha production by human mononuclear cells.
Cannabinoids are known to downregulate immune response but the role for cannabinoid receptors in cannabinoid-induced immunosuppression is still unclear. To address this question, the interference of CB1 and CB2 receptor antagonists with the inhibition of TNF-alpha production by synthetic cannabinoid WIN 55,212-2 was studied using human peripheral blood mononuclear cells (PBMC) in vitro. CB2 (SR 144528) but not CB1 (SR 141716A) receptor antagonist dose dependently interfered with WIN 55,212-2-induced inhibition of TNF-alpha synthesis. Also, WIN 55,212-2 decreased fMLP-induced reactive oxygen species generation in lipopolysaccharide (LPS)-primed PBMC. However, the high concentrations of cannabinoid receptor ligands needed to achieve significant effects suggest that the observed effects may be in part cannabinoid receptor independent.
Germain
Noëlla
N
INSERM U456, IFR 97, Université de Rennes 1, 2, France.
Boichot
Elisabeth
E
Advenier
Charles
C
Berdyshev
Evgueni V
EV
Lagente
Vincent
V
D048588:Benzoxazines; D001892:Camphanes / Q000494:pharmacology; D002186:Cannabinoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D009025:Morpholines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009281:Naphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant; D013481:Superoxides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects
D048588:Benzoxazines; D001892:Camphanes; D002186:Cannabinoids; D008024:Ligands; D008070:Lipopolysaccharides; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; C110630:SR 144528; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D000077285:Rimonabant