Toluene diisocyanate (TDI)-induced asthma is an inflammatory disease of the airways characterized by airway remodeling 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. Objective 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 hours after TDI inhalation and continued for up to 72 hours. 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. In addition, the molar ratio of MMP-9/TIMP-1 significantly decreased at 7 hours after TDI inhalation and continued up to 72 hours.CONCLUSIONS: These data suggest that airway inflammation is associated with an imbalance between MMP-9 and TIMP-1
These data may play an important role in the pathogenesis of TDI-induced asthma
E. Choi, None.