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    Beneficial effects of cannabinoids (CB) in a murine model of allergen-induced airway inflammation: role of CB1/CB2 receptors.

    Abstract

    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.

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    Authors+Show Affiliations

    Braun A
    ,

    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

    Engel T
    ,
    Aguilar-Pimentel JA
    ,
    Zimmer A
    ,
    Jakob T
    ,
    Behrendt H
    ,
    Mempel M

    Source

    Immunobiology 216:4 2011 Apr pg 466-76

    MeSH

    Allergens
    Animals
    Bronchoalveolar Lavage Fluid
    Cannabinoids
    Cytokines
    Disease Models, Animal
    Female
    Immunization
    Immunoglobulins
    Inflammation
    Leukocytes
    Mice
    Mice, Inbred C57BL
    Mice, Knockout
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2
    Respiratory Tract Diseases
    Spleen
    Th2 Cells

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21056512

    Citation

    TY - JOUR T1 - Beneficial effects of cannabinoids (CB) in a murine model of allergen-induced airway inflammation: role of CB1/CB2 receptors. AU - Braun,Andrea, AU - Engel,Tabea, AU - Aguilar-Pimentel,Juan Antonio, AU - Zimmer,Andreas, AU - Jakob,Thilo, AU - Behrendt,Heidrun, AU - Mempel,Martin, Y1 - 2010/09/18/ PY - 2010/8/12/received PY - 2010/9/13/revised PY - 2010/9/14/accepted PY - 2010/9/18/aheadofprint PY - 2010/11/9/entrez PY - 2010/11/9/pubmed PY - 2011/9/29/medline SP - 466 EP - 76 JF - Immunobiology JO - Immunobiology VL - 216 IS - 4 N2 - 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. SN - 1878-3279 UR - https://www.unboundmedicine.com/medline/citation/21056512/abstract/Beneficial_effects_of_cannabinoids__CB__in_a_murine_model_of_allergen_induced_airway_inflammation:_Role_of_CB_1_/CB_2__receptors_ L2 - http://linkinghub.elsevier.com/retrieve/pii/S0171-2985(10)00159-2 ER -