[en] 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. Allergenexposed
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.
Guéders, Maud ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Hirst, S.
Quesada Calvo, Florence ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Département des sciences biomédicales et précliniques
Paulissen, Geneviève ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Hacha, Jonathan ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Gilles, Christine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Gosset, P.
Louis, Renaud ; Université de Liège - ULiège > Département des sciences cliniques > Pneumologie - Allergologie
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement
Lopez-Otin, C.
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Cataldo, Didier ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, humaines et path.
Language :
English
Title :
MMP-19 Deficiency Promotes Tenascin-C Accumulation and Allergen-induced Airway Inflammation.
Publication date :
2010
Journal title :
American Journal of Respiratory Cell and Molecular Biology
ISSN :
1044-1549
eISSN :
1535-4989
Publisher :
American Thoracic Society, New York, United States - New York
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
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