دورية أكاديمية
MMP-1 activation contributes to airway smooth muscle growth and asthma severity
| العنوان: | MMP-1 activation contributes to airway smooth muscle growth and asthma severity |
|---|---|
| المؤلفون: | Naveed, SU, Clements, D, Jackson, DJ, Philp, C, Billington, CK, Soomro, I, Reynolds, C, Harrison, TW, Johnston, SL, Shaw, DE, Johnson, SR |
| المساهمون: | Commission of the European Communities, Asthma UK, Medical Research Council (MRC), National Institute for Health Research |
| المصدر: | 1009 ; 1000 |
| بيانات النشر: | American Thoracic Society |
| سنة النشر: | 2016 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | Science & Technology, Life Sciences & Biomedicine, Critical Care Medicine, Respiratory System, General & Internal Medicine, asthma, extracellular matrix, airway remodeling, airway smooth muscle, mast cells, EXTRACELLULAR-MATRIX, SERINE PROTEASES, CHILDHOOD ASTHMA, MAST-CELLS, IN-VITRO, PROLIFERATION, INFLAMMATION, COLLAGENASE, OBSTRUCTION, BRONCHOCONSTRICTION, Adult, Bronchi, Bronchial Hyperreactivity, Bronchial Provocation Tests, Cell Culture Techniques, Female, Humans, Male, Matrix Metalloproteinase 1, Muscle |
| جغرافية الموضوع: | United States |
| الوصف: | INTRODUCTION: Matrix metalloproteinase-1 and mast cells are present in the airways of people with asthma. We hypothesised that matrix metalloproteinase-1 could be activated by mast cells and increase asthma severity. METHODS: Patients with stable asthma and healthy controls underwent spirometry, methacholine challenge, bronchoscopy and their airway smooth muscle cells were grown in culture. A second asthma group and controls had symptom scores, spirometry and bronchoalveolar lavage before and after rhinovirus-induced asthma exacerbations. Extra-cellular matrix was prepared from decellularised airway smooth muscle cultures. Matrix metalloproteinase-1 protein and activity were assessed. RESULTS: Airway smooth muscle cells generated pro-matrix metalloproteinase-1 which was proteolytically activated by mast cell tryptase. Airway smooth muscle treated with activated mast cell supernatants produced extra-cellular matrix which enhanced subsequent airway smooth muscle growth by 1.5 fold (p<0.05) which was dependent on matrix metalloproteinase-1 activation. In asthma, airway pro-matrix metalloproteinase-1 was 5.4 fold higher than control subjects (p=0.002). Mast cell numbers were associated with airway smooth muscle proliferation and matrix metalloproteinase-1 protein associated with bronchial hyper-responsiveness. During exacerbations, matrix metalloproteinase-1 activity increased and was associated with fall in FEV1 and worsening asthma symptoms. CONCLUSIONS: Matrix metalloproteinase-1 is activated by mast cell tryptase resulting in a pro-proliferative extra-cellular matrix. In asthma, mast cells are associated with airway smooth muscle growth, matrix metalloproteinase-1 levels are associated with bronchial hyper-responsiveness and matrix metalloproteinase-1 activation with exacerbation severity. Our findings suggest that airway smooth muscle/mast cell interactions contribute to asthma severity by transiently increasing matrix metalloproteinase activation, airway smooth muscle growth and airway responsiveness. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1535-4970 |
| العلاقة: | American Journal of Respiratory and Critical Care Medicine; http://hdl.handle.net/10044/1/44587Test; https://dx.doi.org/10.1164/rccm.201604-0822OCTest; 233015; CH11SJ; G1000758; NF-SI-0514-10092 |
| DOI: | 10.1164/rccm.201604-0822OC |
| الإتاحة: | https://doi.org/10.1164/rccm.201604-0822OCTest http://hdl.handle.net/10044/1/44587Test |
| حقوق: | © 2016 American Thoracic Society |
| رقم الانضمام: | edsbas.3304AAA1 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15354970 |
|---|---|
| DOI: | 10.1164/rccm.201604-0822OC |