Role of cannabinoid receptors in Delta-9-tetrahydrocannabinol suppression of IL-12p40 in mouse bone marrow-derived dendritic cells infected with Legionella pneumophila

• Published in: European journal of pharmacology 2006-02, Vol.532 (1), p.170-177
• Main Authors: Lu, Tangying, Newton, Cathy, Perkins, Izabella, Friedman, Herman, Klein, Thomas W.
• Format: Article
• Language: English
• Subjects: 2-arachidonoylglycerol; Animals; Biological and medical sciences; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Bone Marrow Cells - microbiology; Cannabinoids; Capsaicin - analogs & derivatives; Capsaicin - pharmacology; Cells, Cultured; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Dendritic Cells - microbiology; Dose-Response Relationship, Drug; Dronabinol - pharmacology; Enzyme-Linked Immunosorbent Assay; Gene Expression - drug effects; Hallucinogens - pharmacology; IL-12; Interleukin-12 - metabolism; Legionella pneumophila; Legionella pneumophila - growth & development; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Pertussis Toxin - pharmacology; Pharmacology. Drug treatments; Protein Subunits - metabolism; Receptor, Cannabinoid, CB1 - genetics; Receptor, Cannabinoid, CB1 - physiology; Receptor, Cannabinoid, CB2 - genetics; Receptor, Cannabinoid, CB2 - physiology; Receptors, Cannabinoid - genetics; Receptors, Cannabinoid - physiology; RNA, Messenger - genetics; RNA, Messenger - metabolism; TRPV Cation Channels - antagonists & inhibitors; TRPV Cation Channels - physiology; Vanilloid receptor
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2005.12.040

Delta-9-tetrahydrocannabinol (THC) injection suppresses serum interleukin-12 (IL-12) levels in Legionella pneumophila-infected mice. Dendritic cells are a major producer of IL-12 and mouse, bone marrow-derived dendritic cell cultures produced high levels of the IL-12p40 following L. pneumophila infection. Treatment with THC suppressed this cytokine response in a concentration-dependent manner and the endocannabinoid, 2-arachidonoyolglycerol, less potently suppressed cytokine production. Dendritic cells expressed mRNA for cannabinoid receptor 1 (CB 1), cannabinoid CB 2 receptor, and vanilloid receptor 1 (TRPV1) and the addition of the G i inhibitor, pertussis toxin, completely attenuated suppression induced by 3 and 6 μM THC but not by 10 μM THC. Furthermore, THC suppression was partially attenuated in dendritic cells from cannabinoid CB 1 receptor and CB 2 receptor knockout mice and in dendritic cells co-treated with THC and cannabinoid receptor antagonists. Cytokine suppression was not attenuated by pretreatment with the TRPV1 antagonist, capsazepine. These results suggest that THC-induced suppression of serum IL-12 is partly due to a suppression of IL-12 production by dendritic cells and that G i signaling and cannabinoid receptors, but not TRPV1, are involved in this suppressive effect.