Role of cannabinoid receptors in Delta-9-tetrahydrocannabinol suppression of IL-12p40 in mouse bone marrow-derived dendritic cells infected with Legionella pneumophila.
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 muM THC but not by 10 muM 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.
Lu
Tangying
T
Department of Medical Microbiology and Immunology, MDC 10 University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA.
Newton
Cathy
C
Perkins
Izabella
I
Friedman
Herman
H
Klein
Thomas W
TW
D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D006213:Hallucinogens / Q000494:pharmacology; D018664:Interleukin-12 / Q000378:metabolism*; D016952:Legionella pneumophila / Q000254:growth & development*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D037342:Pertussis Toxin / Q000494:pharmacology; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000502:physiology; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000502:physiology; D043882:Receptors, Cannabinoid / Q000235:genetics / Q000502:physiology*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000502:physiology
D006213:Hallucinogens; D021122:Protein Subunits; D012333:RNA, Messenger; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D018664:Interleukin-12; D013759:Dronabinol; D037342:Pertussis Toxin; C071423:capsazepine; D002211:Capsaicin