Sputum matrix metalloproteinase-9: tissue inhibitor of metalloproteinase-1 ratio in acute asthma.
BACKGROUND
The ratio of matrix metalloproteinase-9 (MMP-9) and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) may be a marker of the balance between airway tissue destruction and repair. TIMP-1 may potentially contribute to the pathogenesis of increased submucosal extracellular matrix deposition in asthma.


OBJECTIVE
Our purpose was to assess the variation in sputum MMP-9 and TIMP-1 during acute asthma.


METHODS
We evaluated the MMP-9 and TIMP-1 balance in sputa of 16 asthmatic patients admitted with spontaneous exacerbation, conducting measurement before (day 1) and after methylprednisolone infusion therapy (days 2, 3, 5, and 7), and on remission days.


RESULTS
Peak expiratory flow and eosinophilic cationic protein levels were significantly (P <.05) improved within 7 days in all patients. Sputum MMP-9 levels on day 2 tended to be lower than on day 1, but not significantly. Zymography revealed that the main enzyme was identified immunologically as MMP-9, and gelatinase activity on day 1 had a tendency to decrease for the following 7 days. The TIMP-1 levels gradually increased until day 5, were significantly (P <.05) high on day 5, and decreased on day 7. The MMP-9/TIMP-1 molar ratios were significantly (P <.05) decreased on days 2, 3, 5, and 7 compared with day 1. Sputum levels of MMP-9 and TIMP-1 and the MMP-9/TIMP-1 molar ratios on day 1 were significantly higher (P <.02) than those on remission days.


CONCLUSIONS
An imbalance between MMP-9 and TIMP-1 was present in acute asthma, with an excess of MMP-9 resulting in a high ratio of MMP-9/TIMP-1 before treatment, and over time with glucocorticosteroid the TIMP-1 levels rose, dropping the ratio of MMP-9/TIMP-1. It was suggested that overproduction of MMP-9 and TIMP-1 after asthma exacerbation might contribute significantly to airway tissue remodeling and that TIMP-1 production in acute asthma might not be suppressed by glucocorticosteroid.
Tanaka
H
H
Third Department of Internal Medicine, Sapporo Medical University School of Medicine, and the Sapporo Hospital of Hokkaido Railway Company, Sapporo, Japan.
Miyazaki
N
N
Oashi
K
K
Tanaka
S
S
Ohmichi
M
M
Abe
S
S
D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D001798:Blood Proteins / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000737:chemistry; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000302:isolation & purification*; D008875:Middle Aged; D012260:Ribonucleases; D013183:Sputum / Q000201:enzymology*; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis
D000305:Adrenal Cortex Hormones; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D018836:Inflammation Mediators; D019715:Tissue Inhibitor of Metalloproteinase-1; D012260:Ribonucleases; D020780:Matrix Metalloproteinase 9