Matrix metalloproteinase-9 expression in asthma: effect of asthma severity, allergen challenge, and inhaled corticosteroids.
BACKGROUND
Asthma is associated with remodeling of the extracellular matrix (ECM) and increased airway obstruction, and the mechanisms of this process are unknown. Matrix metalloproteinases (MMPs) are a group of enzymes capable of degrading the ECM. They are released along with their inhibitors, tissue inhibitor of MMP (TIMP).


OBJECTIVE
s: To determine whether severe, persistent asthma is associated with increased levels of MMP-9 in the airway compared with mild asthma, and to assess the effect of both allergen exposure and steroid treatment on MMP-9 and TIMP-1 levels.


METHODS
Prospective analysis of levels and activity of MMP-9 and TIMP-1 in BAL fluid (BALF) and induced sputum obtained from asthmatics of differing disease severity. In patients with mild asthma, MMP-9 and TIMP-1 levels were studied in induced sputum following allergen challenge and in BALF after inhaled steroid therapy.


METHODS
Eighteen patients with mild asthma, 10 patients with severe asthma, and 10 nonsmoking, atopic subjects had their sputum studied. Fourteen of the patients with mild asthma underwent allergen challenge. BAL was collected from 16 patients with mild asthma before and after 4 weeks treatment with inhaled budesonide, 800 micro g bid, or placebo.


RESULTS
Patients with severe asthma had increased levels and activity of sputum MMP-9 in their sputum compared with patients with mild asthma and normal subjects. Allergen challenge increased the MMP-9/TIMP-1 ratio and MMP-9 activity. Inhaled budesonide had no effect on MMP-9 or TIMP-1 in patients with mild asthma.


CONCLUSIONS
MMP-9 may play a role in chronic airway inflammation and remodeling in asthma, as concentrations are increased in severe, persistent asthma and following allergen challenge. Inhaled steroids may not affect MMP-9 and TIMP in patients with mild asthma, and additional studies in patients with more severe asthma are needed.
Mattos
Waldo
W
Department of Thoracic Medicine, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, UK.
Lim
Sam
S
Russell
Richard
R
Jatakanon
Anon
A
Chung
K Fan
KF
Barnes
Peter J
PJ
D000280:Administration, Inhalation; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy / Q000201:enzymology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D019819:Budesonide / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D008875:Middle Aged; D012720:Severity of Illness Index; D013183:Sputum / Q000737:chemistry; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D019819:Budesonide; D020780:Matrix Metalloproteinase 9