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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2010-8-20
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pubmed:abstractText |
Matrix metalloproteinases (MMPs) recently appeared as key regulators of inflammation, allowing the recruitment and clearance of inflammatory cells and modifying the biological activity of many peptide mediators by cleavage. MMP-19 is newly described, and it preferentially cleaves matrix proteins such as collagens and tenascin-C. The role of MMP-19 in asthma has not been described to date. The present study sought to assess the expression of MMP-19 in a murine asthma model, and to address the biological effects of MMP-19 deficiency in mice. Allergen-exposed, wild-type mice displayed increased expression of MMP-19 mRNA and an increased number of MMP-19-positive cells in the lungs, as detected by immunohistochemistry. After an allergen challenge of MMP-19 knockout (MMP-19(-/-)) mice, exacerbated eosinophilic inflammation was detected in bronchoalveolar lavage fluid and bronchial tissue, along with increased airway responsiveness to methacholine. A shift toward increased T helper-2 lymphocyte (Th2)-driven inflammation in MMP-19(-/-) mice was demonstrated by (1) increased numbers of cells expressing the IL-33 receptor T(1)/ST(2) in lung parenchyma, (2) increased IgG(1) levels in serum, and (3) higher levels of IL-13 and eotaxin-1 in lung extracts. Tenascin-C was found to accumulate in peribronchial areas of MMP-19(-/-) after allergen challenges, as assessed by Western blot and immunohistochemistry analyses. 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 may act on Th2 inflammation homeostasis by preventing the accumulation of tenascin protein.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1535-4989
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pubmed:author |
pubmed-author:CataldoDidier DDD,
pubmed-author:FoidartJean-MichelJM,
pubmed-author:GillesChristineC,
pubmed-author:GossetPhilippeP,
pubmed-author:GuedersMaud MMM,
pubmed-author:HachaJonathanJ,
pubmed-author:HirstStuart JSJ,
pubmed-author:Lopez-OtinCarlosC,
pubmed-author:LouisRenaudR,
pubmed-author:NoëlAgnesA,
pubmed-author:PaulissenGenevièveG,
pubmed-author:Quesada-CalvoFlorenceF
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pubmed:issnType |
Electronic
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
286-95
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pubmed:meshHeading |
pubmed-meshheading:19843707-Adult,
pubmed-meshheading:19843707-Allergens,
pubmed-meshheading:19843707-Animals,
pubmed-meshheading:19843707-Asthma,
pubmed-meshheading:19843707-Blotting, Western,
pubmed-meshheading:19843707-Bone Marrow,
pubmed-meshheading:19843707-Bronchial Hyperreactivity,
pubmed-meshheading:19843707-Bronchoalveolar Lavage Fluid,
pubmed-meshheading:19843707-Cells, Cultured,
pubmed-meshheading:19843707-Eosinophils,
pubmed-meshheading:19843707-Female,
pubmed-meshheading:19843707-Flow Cytometry,
pubmed-meshheading:19843707-Humans,
pubmed-meshheading:19843707-Immunoenzyme Techniques,
pubmed-meshheading:19843707-Interleukin-13,
pubmed-meshheading:19843707-Lung,
pubmed-meshheading:19843707-Male,
pubmed-meshheading:19843707-Matrix Metalloproteinases, Secreted,
pubmed-meshheading:19843707-Mice,
pubmed-meshheading:19843707-Mice, Knockout,
pubmed-meshheading:19843707-Myocytes, Smooth Muscle,
pubmed-meshheading:19843707-RNA, Messenger,
pubmed-meshheading:19843707-Respiratory System,
pubmed-meshheading:19843707-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19843707-T-Lymphocytes,
pubmed-meshheading:19843707-Tenascin,
pubmed-meshheading:19843707-Th2 Cells
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pubmed:year |
2010
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pubmed:articleTitle |
Matrix metalloproteinase-19 deficiency promotes tenascin-C accumulation and allergen-induced airway inflammation.
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pubmed:affiliation |
Department of Respiratory Diseases, University of Liege and Centre Hospitalier Universitaire, Belgium.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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