Matrix metalloproteinase-19 deficiency promotes tenascin-C accumulation and allergen-induced airway inflammation

Maud M Gueders, Stuart John Hirst, Florence Quesada-Calvo, Genevieve Paulissen, Jonathan Hacha, Christine Gilles, Philippe Gosset, Renaud Louis, Jean-Michel Foidart, Carlos Lopez-Otin, Agnes Noel, Didier D Cataldo

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27 Citations (Scopus)


Matrix metalloproteinases (MMPs) recently appeared as key regulators of inflammation, allowing recruitment and clearance of inflammatory cells and modifying the biological activity of many peptidic mediators by cleavage. MMP-19 is a newly described MMP and preferentially cleaves matrix proteins such as collagens and tenascin-C. The role of MMP-19 in asthma has not been described to date. The purpose of the present study was to assess MMP-19 expression in a murine asthma model and to address biological effects of MMP-19 deficiency in mice. Allergen-exposed wild-type (WT) mice displayed an increased expression of MMP-19 mRNA and an increased number of MMP-19-positive cells in the lungs detected by immunohistochemistry. After allergen challenge of MMP-19 knockout (MMP-19-/-) mice, an exacerbated eosinophilic inflammation was detected in bronchoalveolar lavage fluid and bronchial tissue along with an increased airway responsiveness to methacholine. A shift towards increased Th2-driven inflammation in MMP-19-/- mice was demonstrated by 1) increased numbers of cells expressing the IL-33 receptor T1/ST2 in lung parenchyma, 2) increased IgG1 levels in serum and 3) higher levels of IL-13 and CCL11 in lung extracts. Tenascin-C was found accumulated in peribronchial areas of MMP-19-/- after allergen challenges as assessed by Western blot and immunohistochemistry analysis. We conclude that MMP-19 is a new mediator in asthma, preventing tenascin-C accumulation and directly or indirectly controlling Th2-driven airway eosinophilia and airway hyperreactivity . Our data suggest that MMP-19 might act on Th2 inflammation homeostasis through preventing tenascin protein accumulation.
Original languageEnglish
Pages (from-to)286 - 295
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Issue number3
Publication statusPublished - 2010

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