Children with stable asthma have reduced airway matrix metalloproteinase-9 and matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio
- 14 September 2005
- journal article
- research article
- Published by Wiley in Clinical and Experimental Allergy
- Vol. 35 (9) , 1168-1174
- https://doi.org/10.1111/j.1365-2222.2005.02326.x
Abstract
Background Childhood asthma is characterized by inflammation of the airways. Structural changes of the airway wall may also be seen in some children early in the course of the disease. Matrix metalloproteinases (MMPs) are key mediators in the metabolism of the extracellular matrix (ECM). Objective To investigate the balance of MMP‐8, MMP‐9 and tissue inhibitor of metalloproteinases (TIMP)‐1 in the airways of children with asthma. Methods One hundred and twenty‐four children undergoing elective surgical procedures also underwent non‐bronchoscopic bronchoalveolar lavage (BAL). MMP‐8, MMP‐9 and TIMP‐1 were measured by ELISA. Results There was a significant reduction in MMP‐9 in atopic asthmatic children (n=31) compared with normal children (n=30) [median difference: 0.57 ng/mL (95% confidence interval: 0.18–1.1 ng/mL)]. The ratio of MMP‐9 to TIMP‐1 was also reduced in asthmatic children. Levels of all three proteins were significantly correlated to each other and to the relative proportions of particular inflammatory cells in BAL fluid (BALF). Both MMP‐8 and MMP‐9 were moderately strongly correlated to the percentage neutrophil count (r=0.40 and 0.47, respectively, P<0.001). Conclusions An imbalance of MMPs and their inhibitors occurs in children with well‐controlled asthma, which may indicate early derangement of the metabolism of the ECM.Keywords
This publication has 58 references indexed in Scilit:
- Relationship of airway wall thickening to an imbalance between matrix metalloproteinase-9 and its inhibitor in asthmaThorax, 2005
- Both inflammation and remodeling influence nitric oxide output in children with refractory asthmaJournal of Allergy and Clinical Immunology, 2004
- Increased circulating 92 kDa matrix metalloproteinase (MMP-9) activity in exacerbations of asthmaThorax, 2003
- Matrix metalloproteases in BAL fluid of patients with cystic fibrosis and their modulation by treatment with dornase alphaThorax, 2002
- Invited Lecture: Activation of the Epithelial Mesenchymal Trophic Unit in the Pathogenesis of AsthmaInternational Archives of Allergy and Immunology, 2001
- Association of trypsin-2 with activation of gelatinase B and collagenase-2 in human bronchoalveolar lavage fluidin vivoAnnals of Medicine, 2001
- Neutrophil Tissue Inhibitor of Matrix Metalloproteinases-1 Occurs in Novel Vesicles That Do Not Fuse with the PhagosomeJournal of Biological Chemistry, 2000
- Bronchoalveolar lavage in children. ERS Task Force on bronchoalveolar lavage in children. European Respiratory SocietyEuropean Respiratory Journal, 2000
- Evaluation of Censored Data Methods To Allow Statistical Comparisons among Very Small Samples with Below Detection Limit ObservationsEnvironmental Science & Technology, 1998
- Investigating paediatric airways by non-bronchoscopic lavage: normal cellular dataClinical and Experimental Allergy, 1996