Role of Matrix Metalloproteinase in the Pathogenesis of Bronchial Asthma

Lee, Yong Chul

Abstract

BACKGROUND: Toluene diisocyanate(TDI) is a leading cause of occupational asthma. However, the pathogenesis of TDI-induced asthma is largely unknown because there is no suitable animal model. METHODS: We developed a murine model of TDI-induced asthma by performing two sensitization with 3% TDI and one challenge with 1% TDI using ultrasonic nebulization. RESULTS: Similar to occupational asthma in humans, murine TDI-induced asthma includes findings 1) increased inflammatory cells, including neutrophils and eosinophils, 2) histologic changes, including infiltration of inflammatory cells around bronchioles, thickened airway epithelium, contraction of bronchioles, and accumulation of mucus and debris in the bronchioles, 3) increased MMP-9 activity in inflammatory cells in the airway lumen, 4) airway hyperresponsiveness. Administration of an MMP inhibitor, MMPI-I, remarkably reduced all these pathophysiological findings. CONCLUSION: Therefore, we conclude that TDI-induced occupational asthma is associated with the induction of MMP-9 in inflammatory cells, and the inhibition of MMP-9 may be a good therapeutic strategy.