Imbalance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in toluene diisocyanate-induced asthma.

Abstract

Toluene diisocyanate (TDI)-induced asthma is an inflammatory disease of the airways characterized by airway remodelling due, at least in part, to an excess of extracellular matrix deposition in the airway wall. 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. We determined whether an imbalance of the MMP-9 : TIMP-1 molar ratio is present before and/or after challenge with TDI. We used a murine model of TDI-induced asthma to evaluate the MMP-9 and TIMP-1 balance in the lung. The expression of MMP-9 and TIMP-1 mRNAs and proteins in the lungs increased at 7 h after TDI inhalation and continued for up to 72 h. Immunohistochemical and immunocytological analyses in the lungs of TDI-exposed mice revealed increases of immunoreactive MMP-9 and TIMP-1. There were significant correlations between the levels of MMP-9 or TIMP-1 and the number of neutrophils, lymphocytes, or eosinophils. The molar ratio of MMP-9/TIMP-1 significantly decreased at 7 h after TDI inhalation and continued up to 72 h. These data suggest that TDI-induced asthma may be associated with an imbalance between MMP-9 and TIMP-1, which could be useful as a marker of airway inflammation and airway remodelling in this disease.