Abstract
Background: ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin motifs) constitute a family of endopeptidases related to matrix metalloproteinases (MMPs). These proteinases have been largely implicated in tissue remodelling associated to pathological processes. ADAMTS-12 has been identified as an asthma-associated gene in a human genome screening program.
Objective: To investigate potential roles of ADAMTS-12 in experimental models of asthma.
Methods: In our study, two different in vivo protocols of allergen-induced asthma were applied to the recently generated Adamts-12-deficient mice, and corresponding wild-type mice.
Results: The results obtained provide evidence for a protective effect of this enzyme against bronchial inflammation and hyperresponsiveness. In the absence of Adamts-12, challenge with allergens (ovalbumin and house dust mite) led to exacerbated eosinophilic inflammation in the bronchoalveolar lavage fluid (BALF) and in lung tissue, along with airway dysfunction assessed by increased airway responsiveness following methacholine exposure. Furthermore, mast cells counts, ST2 receptor, and IL-33 levels were higher in the lungs of allergen-challenged Adamts-12-deficient mice.
Conclusion: The present study provides the first experimental evidence for a contribution of ADAMTS-12 as a key mediator in asthma, interfering with immunological processes leading to inflammation and airway hyperresponsiveness.
- © 2011 ERS