Beneficial effects of cannabinoids (CB) in a murine model of allergen-induced airway inflammation: role of CB1/CB2 receptors.
The endocannabinoid system (ECS) consists of two cannabinoid (CB) receptors, namely CB(1) and CB(2) receptor, and their endogenous (endocannabinoids) and exogenous (cannabinoids, e.g. delta-9-tetrahydrocannabinol (THC)) ligands which bind to these receptors. Based on studies suggesting a role of THC and the ECS in inflammation, the objective of this study was to examine their involvement in type I hypersensitivity using a murine model of allergic airway inflammation. THC treatment of C57BL/6 wildtype mice dramatically reduced airway inflammation as determined by significantly reduced total cell counts in bronchoalveolar lavage (BAL). These effects were greatest when mice were treated during both, the sensitization and the challenge phase. Furthermore, systemic immune responses were significantly suppressed in mice which received THC during sensitization phase. To investigate a role of CB(1/2) receptors in this setting, we used pharmacological blockade of CB(1) and/or CB(2) receptors by the selective antagonists and moreover CB(1)/CB(2) receptor double-knockout mice (CB(1)(-/-)/CB(2)(-/-)) and found neither significant changes in the cell patterns in BAL nor in immunoglobulin levels as compared to wildtype mice. Our results indicate that the activation of the ECS by applying the agonist THC is involved in the development of type I allergies. However, CB(1)/CB(2) receptor-independent signalling seems likely in the observed results.
ZAUM - Center for Allergy and Environment, Division of Environmental Dermatology and Allergy, Helmholtz Zentrum München/Technische Universität München (TUM), Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany. andrea.braun@helmholtz-muenchen.de
Andrea
A
Braun
Tabea
T
Engel
Juan Antonio
JA
Aguilar-Pimentel
Andreas
A
Zimmer
Thilo
T
Jakob
Heidrun
H
Behrendt
Martin
M
Mempel
D000485:Allergens / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002186:Cannabinoids / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D007136:Immunoglobulins / Q000097:blood; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012140:Respiratory Tract Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology
D000485:Allergens; D002186:Cannabinoids; D016207:Cytokines; D007136:Immunoglobulins; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2