title: Protective effect of a Protein Epitope Mimetic CCR10 antagonist, POL7085, in a model of allergic eosinophilic airway inflammation.
abstract: BACKGROUND
  Potential 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.
  
  
  METHODS
  Mice 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.
  
  
  RESULTS
  Allergen 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 %).
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: 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. daubeuf@unistra.fr.
authors.forename: François
authors.initials: F
authors.lastname: Daubeuf
authors.affiliation: Polyphor Ltd, Hegenheimermattweg 125, CH-4123, Allschwil, Switzerland. francoise.jung@polyphor.com.
authors.forename: Françoise
authors.initials: F
authors.lastname: Jung
authors.affiliation: Polyphor Ltd, Hegenheimermattweg 125, CH-4123, Allschwil, Switzerland. garry.douglas@polyphor.com.
authors.forename: Garry J
authors.initials: GJ
authors.lastname: Douglas
authors.affiliation: Polyphor Ltd, Hegenheimermattweg 125, CH-4123, Allschwil, Switzerland. eric.chevalier@polyphor.com.
authors.forename: Eric
authors.initials: E
authors.lastname: Chevalier
authors.affiliation: 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. nelly.frossard@unistra.fr.
authors.forename: Nelly
authors.initials: N
authors.lastname: Frossard
mesh_terms: D000818:Animals; D001249:Asthma / Q000473:pathology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D000939:Epitopes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011657:Pulmonary Eosinophilia / Q000473:pathology / Q000517:prevention & control*; D054447:Receptors, CCR10 / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: C515707:Ccr10 protein, mouse; D000939:Epitopes; D054447:Receptors, CCR10