Bitter Taste Receptor Agonists Mitigate Features of Allergic Asthma in Mice.
Identifieur interne : 000D28 ( Main/Exploration ); précédent : 000D27; suivant : 000D29Bitter Taste Receptor Agonists Mitigate Features of Allergic Asthma in Mice.
Auteurs : Pawan Sharma [États-Unis] ; Roslyn Yi [États-Unis] ; Ajay P. Nayak [États-Unis] ; Nadan Wang [États-Unis] ; Francesca Tang [Australie] ; Morgan J. Knight [États-Unis] ; Shi Pan [États-Unis] ; Brian Oliver [Australie] ; Deepak A. Deshpande [États-Unis]Source :
- Scientific reports [ 2045-2322 ] ; 2017.
Descripteurs français
- KwdFr :
- Allergènes (immunologie), Animaux, Asthme (), Asthme (immunologie), Asthme (physiopathologie), Asthme (traitement médicamenteux), Chimiotaxie (), Chloroquine (usage thérapeutique), Cytokines (métabolisme), Femelle, Goût, Granulocytes neutrophiles (), Humains, Hyperréactivité bronchique (), Hyperréactivité bronchique (anatomopathologie), Hyperréactivité bronchique (immunologie), Hyperréactivité bronchique (physiopathologie), Hypersensibilité (), Hypersensibilité (immunologie), Hypersensibilité (physiopathologie), Hypersensibilité (traitement médicamenteux), Immunisation, Inflammation (), Inflammation (anatomopathologie), Liquide de lavage bronchoalvéolaire (cytologie), Matrix metalloproteinases (métabolisme), Modèles animaux de maladie humaine, Mucus (métabolisme), Muscles lisses (), Muscles lisses (anatomopathologie), Numération cellulaire, Poumon (anatomopathologie), Poumon (immunologie), Poumon (parasitologie), Poumon (physiopathologie), Pyroglyphidae (), Quinine (usage thérapeutique), Remodelage des voies aériennes (), Récepteurs couplés aux protéines G (agonistes), Récepteurs couplés aux protéines G (métabolisme), Souris de lignée BALB C.
- MESH :
- agonistes : Récepteurs couplés aux protéines G.
- anatomopathologie : Hyperréactivité bronchique, Inflammation, Muscles lisses, Poumon.
- cytologie : Liquide de lavage bronchoalvéolaire.
- immunologie : Allergènes, Asthme, Hyperréactivité bronchique, Hypersensibilité, Poumon.
- métabolisme : Cytokines, Matrix metalloproteinases, Mucus, Récepteurs couplés aux protéines G.
- parasitologie : Poumon.
- physiopathologie : Asthme, Hyperréactivité bronchique, Hypersensibilité, Poumon.
- traitement médicamenteux : Asthme, Hypersensibilité.
- usage thérapeutique : Chloroquine, Quinine.
- Animaux, Asthme, Chimiotaxie, Femelle, Goût, Granulocytes neutrophiles, Humains, Hyperréactivité bronchique, Hypersensibilité, Immunisation, Inflammation, Modèles animaux de maladie humaine, Muscles lisses, Numération cellulaire, Pyroglyphidae, Remodelage des voies aériennes, Souris de lignée BALB C.
English descriptors
- KwdEn :
- Airway Remodeling (drug effects), Allergens (immunology), Animals, Asthma (drug therapy), Asthma (immunology), Asthma (physiopathology), Asthma (prevention & control), Bronchial Hyperreactivity (complications), Bronchial Hyperreactivity (immunology), Bronchial Hyperreactivity (pathology), Bronchial Hyperreactivity (physiopathology), Bronchoalveolar Lavage Fluid (cytology), Cell Count, Chemotaxis (drug effects), Chloroquine (therapeutic use), Cytokines (metabolism), Disease Models, Animal, Female, Humans, Hypersensitivity (drug therapy), Hypersensitivity (immunology), Hypersensitivity (physiopathology), Hypersensitivity (prevention & control), Immunization, Inflammation (complications), Inflammation (pathology), Lung (immunology), Lung (parasitology), Lung (pathology), Lung (physiopathology), Matrix Metalloproteinases (metabolism), Mice, Inbred BALB C, Mucus (metabolism), Muscle, Smooth (drug effects), Muscle, Smooth (pathology), Neutrophils (drug effects), Pyroglyphidae (drug effects), Quinine (therapeutic use), Receptors, G-Protein-Coupled (agonists), Receptors, G-Protein-Coupled (metabolism), Taste.
- MESH :
- chemical , agonists : Receptors, G-Protein-Coupled.
- chemical , immunology : Allergens.
- complications : Bronchial Hyperreactivity, Inflammation.
- cytology : Bronchoalveolar Lavage Fluid.
- drug effects : Airway Remodeling, Chemotaxis, Muscle, Smooth, Neutrophils, Pyroglyphidae.
- drug therapy : Asthma, Hypersensitivity.
- immunology : Asthma, Bronchial Hyperreactivity, Hypersensitivity, Lung.
- chemical , metabolism : Cytokines, Matrix Metalloproteinases, Mucus, Receptors, G-Protein-Coupled.
- parasitology : Lung.
- pathology : Bronchial Hyperreactivity, Inflammation, Lung, Muscle, Smooth.
- physiopathology : Asthma, Bronchial Hyperreactivity, Hypersensitivity, Lung.
- prevention & control : Asthma, Hypersensitivity.
- chemical , therapeutic use : Chloroquine, Quinine.
- Animals, Cell Count, Disease Models, Animal, Female, Humans, Immunization, Mice, Inbred BALB C, Taste.
Abstract
Asthma is characterized by airway inflammation, mucus secretion, remodeling and hyperresponsiveness (AHR). Recent research has established the bronchodilatory effect of bitter taste receptor (TAS2R) agonists in various models. Comprehensive pre-clinical studies aimed at establishing effectiveness of TAS2R agonists in disease models are lacking. Here we aimed to determine the effect of TAS2R agonists on features of asthma. Further, we elucidated a mechanism by which TAS2R agonists mitigate features of asthma. Asthma was induced in mice using intranasal house dust mite or aerosol ova-albumin challenge, and chloroquine or quinine were tested in both prophylactic and treatment models. Allergen challenge resulted in airway inflammation as evidenced by increased immune cells infiltration and release of cytokines and chemokines in the lungs, which were significantly attenuated in TAS2R agonists treated mice. TAS2R agonists attenuated features of airway remodeling including smooth muscle mass, extracellular matrix deposition and pro-fibrotic signaling, and also prevented mucus accumulation and development of AHR in mice. Mechanistic studies using human neutrophils demonstrated that inhibition of immune cell chemotaxis is a key mechanism by which TAS2R agonists blocked allergic airway inflammation and exerted anti-asthma effects. Our comprehensive studies establish the effectiveness of TAS2R agonists in mitigating multiple features of allergic asthma.
DOI: 10.1038/srep46166
PubMed: 28397820
Affiliations:
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Le document en format XML
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Nayak</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, 19107, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, 19107</wicri:regionArea><wicri:noRegion>19107</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Nadan" sort="Wang, Nadan" uniqKey="Wang N" first="Nadan" last="Wang">Nadan Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, 19107, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, 19107</wicri:regionArea><wicri:noRegion>19107</wicri:noRegion></affiliation></author><author><name sortKey="Tang, Francesca" sort="Tang, Francesca" uniqKey="Tang F" first="Francesca" last="Tang">Francesca Tang</name><affiliation wicri:level="1"><nlm:affiliation>Respiratory Research Group, Woolcock Institute of Medical Research and School of Life Sciences, University of Technology, Sydney, NSW, 2007, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Respiratory Research Group, Woolcock Institute of Medical Research and School of Life Sciences, University of Technology, Sydney, NSW, 2007</wicri:regionArea><wicri:noRegion>2007</wicri:noRegion></affiliation></author><author><name sortKey="Knight, Morgan J" sort="Knight, Morgan J" uniqKey="Knight M" first="Morgan J" last="Knight">Morgan J. Knight</name><affiliation wicri:level="1"><nlm:affiliation>Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, 77054, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, 77054</wicri:regionArea><wicri:noRegion>77054</wicri:noRegion></affiliation></author><author><name sortKey="Pan, Shi" sort="Pan, Shi" uniqKey="Pan S" first="Shi" last="Pan">Shi Pan</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, 19107, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, 19107</wicri:regionArea><wicri:noRegion>19107</wicri:noRegion></affiliation></author><author><name sortKey="Oliver, Brian" sort="Oliver, Brian" uniqKey="Oliver B" first="Brian" last="Oliver">Brian Oliver</name><affiliation wicri:level="1"><nlm:affiliation>Respiratory Research Group, Woolcock Institute of Medical Research and School of Life Sciences, University of Technology, Sydney, NSW, 2007, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Respiratory Research Group, Woolcock Institute of Medical Research and School of Life Sciences, University of Technology, Sydney, NSW, 2007</wicri:regionArea><wicri:noRegion>2007</wicri:noRegion></affiliation></author><author><name sortKey="Deshpande, Deepak A" sort="Deshpande, Deepak A" uniqKey="Deshpande D" first="Deepak A" last="Deshpande">Deepak A. Deshpande</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, 19107, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Medicine, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, 19107</wicri:regionArea><wicri:noRegion>19107</wicri:noRegion></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Airway Remodeling (drug effects)</term><term>Allergens (immunology)</term><term>Animals</term><term>Asthma (drug therapy)</term><term>Asthma (immunology)</term><term>Asthma (physiopathology)</term><term>Asthma (prevention & control)</term><term>Bronchial Hyperreactivity (complications)</term><term>Bronchial Hyperreactivity (immunology)</term><term>Bronchial Hyperreactivity (pathology)</term><term>Bronchial Hyperreactivity (physiopathology)</term><term>Bronchoalveolar Lavage Fluid (cytology)</term><term>Cell Count</term><term>Chemotaxis (drug effects)</term><term>Chloroquine (therapeutic use)</term><term>Cytokines (metabolism)</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Hypersensitivity (drug therapy)</term><term>Hypersensitivity (immunology)</term><term>Hypersensitivity (physiopathology)</term><term>Hypersensitivity (prevention & control)</term><term>Immunization</term><term>Inflammation (complications)</term><term>Inflammation (pathology)</term><term>Lung (immunology)</term><term>Lung (parasitology)</term><term>Lung (pathology)</term><term>Lung (physiopathology)</term><term>Matrix Metalloproteinases (metabolism)</term><term>Mice, Inbred BALB C</term><term>Mucus (metabolism)</term><term>Muscle, Smooth (drug effects)</term><term>Muscle, Smooth (pathology)</term><term>Neutrophils (drug effects)</term><term>Pyroglyphidae (drug effects)</term><term>Quinine (therapeutic use)</term><term>Receptors, G-Protein-Coupled (agonists)</term><term>Receptors, G-Protein-Coupled (metabolism)</term><term>Taste</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Allergènes (immunologie)</term><term>Animaux</term><term>Asthme ()</term><term>Asthme (immunologie)</term><term>Asthme (physiopathologie)</term><term>Asthme (traitement médicamenteux)</term><term>Chimiotaxie ()</term><term>Chloroquine (usage thérapeutique)</term><term>Cytokines (métabolisme)</term><term>Femelle</term><term>Goût</term><term>Granulocytes neutrophiles ()</term><term>Humains</term><term>Hyperréactivité bronchique ()</term><term>Hyperréactivité bronchique (anatomopathologie)</term><term>Hyperréactivité bronchique (immunologie)</term><term>Hyperréactivité bronchique (physiopathologie)</term><term>Hypersensibilité ()</term><term>Hypersensibilité (immunologie)</term><term>Hypersensibilité (physiopathologie)</term><term>Hypersensibilité (traitement médicamenteux)</term><term>Immunisation</term><term>Inflammation ()</term><term>Inflammation (anatomopathologie)</term><term>Liquide de lavage bronchoalvéolaire (cytologie)</term><term>Matrix metalloproteinases (métabolisme)</term><term>Modèles animaux de maladie humaine</term><term>Mucus (métabolisme)</term><term>Muscles lisses ()</term><term>Muscles lisses (anatomopathologie)</term><term>Numération cellulaire</term><term>Poumon (anatomopathologie)</term><term>Poumon (immunologie)</term><term>Poumon (parasitologie)</term><term>Poumon (physiopathologie)</term><term>Pyroglyphidae ()</term><term>Quinine (usage thérapeutique)</term><term>Remodelage des voies aériennes ()</term><term>Récepteurs couplés aux protéines G (agonistes)</term><term>Récepteurs couplés aux protéines G (métabolisme)</term><term>Souris de lignée BALB C</term></keywords><keywords scheme="MESH" type="chemical" qualifier="agonists" xml:lang="en"><term>Receptors, G-Protein-Coupled</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Allergens</term></keywords><keywords scheme="MESH" qualifier="agonistes" xml:lang="fr"><term>Récepteurs couplés aux protéines G</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Hyperréactivité bronchique</term><term>Inflammation</term><term>Muscles lisses</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Bronchial Hyperreactivity</term><term>Inflammation</term></keywords><keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Liquide de lavage bronchoalvéolaire</term></keywords><keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Bronchoalveolar Lavage Fluid</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Airway Remodeling</term><term>Chemotaxis</term><term>Muscle, Smooth</term><term>Neutrophils</term><term>Pyroglyphidae</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Asthma</term><term>Hypersensitivity</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Allergènes</term><term>Asthme</term><term>Hyperréactivité bronchique</term><term>Hypersensibilité</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Asthma</term><term>Bronchial Hyperreactivity</term><term>Hypersensitivity</term><term>Lung</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cytokines</term><term>Matrix Metalloproteinases</term><term>Mucus</term><term>Receptors, G-Protein-Coupled</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Cytokines</term><term>Matrix metalloproteinases</term><term>Mucus</term><term>Récepteurs couplés aux protéines G</term></keywords><keywords scheme="MESH" qualifier="parasitologie" xml:lang="fr"><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="parasitology" xml:lang="en"><term>Lung</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Bronchial Hyperreactivity</term><term>Inflammation</term><term>Lung</term><term>Muscle, Smooth</term></keywords><keywords scheme="MESH" qualifier="physiopathologie" xml:lang="fr"><term>Asthme</term><term>Hyperréactivité bronchique</term><term>Hypersensibilité</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Asthma</term><term>Bronchial Hyperreactivity</term><term>Hypersensitivity</term><term>Lung</term></keywords><keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Asthma</term><term>Hypersensitivity</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Chloroquine</term><term>Quinine</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Asthme</term><term>Hypersensibilité</term></keywords><keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Chloroquine</term><term>Quinine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Count</term><term>Disease Models, Animal</term><term>Female</term><term>Humans</term><term>Immunization</term><term>Mice, Inbred BALB C</term><term>Taste</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Asthme</term><term>Chimiotaxie</term><term>Femelle</term><term>Goût</term><term>Granulocytes neutrophiles</term><term>Humains</term><term>Hyperréactivité bronchique</term><term>Hypersensibilité</term><term>Immunisation</term><term>Inflammation</term><term>Modèles animaux de maladie humaine</term><term>Muscles lisses</term><term>Numération cellulaire</term><term>Pyroglyphidae</term><term>Remodelage des voies aériennes</term><term>Souris de lignée BALB C</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Asthma is characterized by airway inflammation, mucus secretion, remodeling and hyperresponsiveness (AHR). Recent research has established the bronchodilatory effect of bitter taste receptor (TAS2R) agonists in various models. Comprehensive pre-clinical studies aimed at establishing effectiveness of TAS2R agonists in disease models are lacking. Here we aimed to determine the effect of TAS2R agonists on features of asthma. Further, we elucidated a mechanism by which TAS2R agonists mitigate features of asthma. Asthma was induced in mice using intranasal house dust mite or aerosol ova-albumin challenge, and chloroquine or quinine were tested in both prophylactic and treatment models. Allergen challenge resulted in airway inflammation as evidenced by increased immune cells infiltration and release of cytokines and chemokines in the lungs, which were significantly attenuated in TAS2R agonists treated mice. TAS2R agonists attenuated features of airway remodeling including smooth muscle mass, extracellular matrix deposition and pro-fibrotic signaling, and also prevented mucus accumulation and development of AHR in mice. Mechanistic studies using human neutrophils demonstrated that inhibition of immune cell chemotaxis is a key mechanism by which TAS2R agonists blocked allergic airway inflammation and exerted anti-asthma effects. Our comprehensive studies establish the effectiveness of TAS2R agonists in mitigating multiple features of allergic asthma.</div></front></TEI><affiliations><list><country><li>Australie</li><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Sharma, Pawan" sort="Sharma, Pawan" uniqKey="Sharma P" first="Pawan" last="Sharma">Pawan Sharma</name></noRegion><name sortKey="Deshpande, Deepak A" sort="Deshpande, Deepak A" uniqKey="Deshpande D" first="Deepak A" last="Deshpande">Deepak A. Deshpande</name><name sortKey="Knight, Morgan J" sort="Knight, Morgan J" uniqKey="Knight M" first="Morgan J" last="Knight">Morgan J. Knight</name><name sortKey="Nayak, Ajay P" sort="Nayak, Ajay P" uniqKey="Nayak A" first="Ajay P" last="Nayak">Ajay P. Nayak</name><name sortKey="Pan, Shi" sort="Pan, Shi" uniqKey="Pan S" first="Shi" last="Pan">Shi Pan</name><name sortKey="Wang, Nadan" sort="Wang, Nadan" uniqKey="Wang N" first="Nadan" last="Wang">Nadan Wang</name><name sortKey="Yi, Roslyn" sort="Yi, Roslyn" uniqKey="Yi R" first="Roslyn" last="Yi">Roslyn Yi</name></country><country name="Australie"><noRegion><name sortKey="Tang, Francesca" sort="Tang, Francesca" uniqKey="Tang F" first="Francesca" last="Tang">Francesca Tang</name></noRegion><name sortKey="Oliver, Brian" sort="Oliver, Brian" uniqKey="Oliver B" first="Brian" last="Oliver">Brian Oliver</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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