title: Control of allergen-induced inflammation and hyperresponsiveness by the metalloproteinase ADAMTS-12.
abstract: A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) constitute a family of endopeptidases related to matrix metalloproteinases. These proteinases have been largely implicated in tissue remodeling associated with pathological processes. Among them, ADAMTS12 was identified as an asthma-associated gene in a human genome screening program. However, its functional implication in asthma is not yet documented. The present study aims at investigating potential ADAMTS-12 functions in experimental models of allergic airways disease. Two different in vivo protocols of allergen-induced airways disease were applied to the recently generated Adamts12-deficient mice and corresponding wild-type mice. In this study, we provide evidence for a protective effect of ADAMTS-12 against bronchial inflammation and hyperresponsiveness. In the absence of Adamts12, challenge with different allergens (OVA and house dust mite) led to exacerbated eosinophilic inflammation in the bronchoalveolar lavage fluid and in lung tissue, along with airway dysfunction assessed by increased airway responsiveness following methacholine exposure. Furthermore, mast cell counts and ST2 receptor and IL-33 levels were higher in the lungs of allergen-challenged Adamts12-deficient mice. The present study provides, to our knowledge, the first experimental evidence for a contribution of ADAMTS-12 as a key mediator in airways disease, interfering with immunological processes leading to inflammation and airway hyperresponsiveness.
authors.affiliation: Laboratory of Tumor and Developmental Biology, Interdisciplinary Group of Applied Genoproteomics-Cancer (GIGA-Cancer), University of Liège and University Hospital of Liège, 4000 Liège, Belgium.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Paulissen
authors.forename: Mehdi
authors.initials: M
authors.lastname: El Hour
authors.forename: Natacha
authors.initials: N
authors.lastname: Rocks
authors.forename: Maud M
authors.initials: MM
authors.lastname: Guéders
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bureau
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopez-Otin
authors.forename: Agnès
authors.initials: A
authors.lastname: Noel
authors.forename: Didier D
authors.initials: DD
authors.lastname: Cataldo
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000633:toxicity*; D000071096:ADAMTS Proteins; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage* / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000276:immunology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D039741:Antigens, Dermatophagoides; D018836:Inflammation Mediators; D010047:Ovalbumin; D051722:ADAM Proteins; D000071096:ADAMTS Proteins; C550048:Adamts12 protein, mouse