Protective effect of a Protein Epitope Mimetic CCR10 antagonist,POL7085, in a model of allergic eosinophilic airway inflammation |
| |
Authors: | Fran?ois Daubeuf Fran?oise Jung Garry J Douglas Eric Chevalier Nelly Frossard |
| |
Institution: | .Laboratoire d’Innovation Thérapeutique, Unité Mixte de Recherche 7200, Centre National de la Recherche Scientifique-Université de Strasbourg and LabEx Medalis, Faculté de Pharmacie, 74, route du Rhin, 67400 Illkirch, France ;.Polyphor Ltd, Hegenheimermattweg 125, CH-4123 Allschwil, Switzerland |
| |
Abstract: | BackgroundPotential involvement of the CCR10/CCL28 axis was recently reported in murine models of allergic asthma. If confirmed, blockade of the CCR10 receptor would represent an alternative to current asthma therapies. We evaluated the effect of a novel Protein Epitope Mimetic CCR10 antagonist, POL7085, in a murine model of allergic eosinophilic airway inflammation.MethodsMice were sensitized and challenged to ovalbumin. POL7085, a CCR10 antagonist (7.5 and 15 mg/kg), dexamethasone (1 mg/kg) or vehicle were administered intranasally once daily 1h before each allergen challenge. On day 21, airway hyperresponsiveness, bronchoalveolar lavage inflammatory cells and Th2 cytokines, and lung tissue mucus and collagen were measured.ResultsAllergen challenge induced airway hyperresponsiveness in vehicle-treated animals as measured by whole body barometric plethysmography, and eosinophilia in bronchoalveolar lavage. POL7085 dose-dependently and significantly decreased airway hyperresponsiveness (34 ± 16 %) and eosinophil numbers in bronchoalveolar lavage (66 ± 6 %). In addition, the highest dose of POL7085 used significantly inhibited lung IL-4 (85 ± 4 %), IL-5 (87 ± 2 %) and IL-13 (190 ± 19 %) levels, and lung collagen (43 ± 11 %).ConclusionsThe Protein Epitope Mimetic CCR10 antagonist, POL7085, significantly and dose-dependently decreased allergen-induced airway hyperresponsiveness and airway inflammation after once daily local treatment. Our data give strong support for further investigations with CCR10 antagonists in asthmatic disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-015-0231-5) contains supplementary material, which is available to authorized users. |
| |
Keywords: | CCR10 CCL28 Asthma Airway hyperresponsiveness Inflammation Mouse Allergen Ovalbumin Eosinophilia |
|
|