Inhibition of matrix metalloproteinases prevents allergen-induced airway inflammation in a murine model of asthma

Although matrix metalloproteinases (MMPs) have been reported to play crucia l roles in the migration of inflammatory cells through basement membrane co mponents in vitro, the role of MMPs in the in vivo accumulation of the cell s to the site of inflammation in bronchial asthma is still obscure, In this study, we investigated the role of MMPs in the pathogenesis of bronchial a sthma, using a murine model of allergic asthma, In this model, we observed the increase of the release of MMP-2 and MMP-9 in bronchoalveolar lavage fl uids after ag inhalation in the mice sensitized with OVA, which was accompa nied by the infiltration of lymphocytes and eosinophils, Administration of tissue inhibitor of metalloproteinase-2 to airways inhibited the Bg-induced infiltration of lymphocytes and eosinophils to airway wall and lumen, redu ced Ag-induced airway hyperresponsiveness, and increased the numbers of eos inophils and lymphocytes in peripheral blood, The inhibition of cellular in filtration to airway lumen was observed also with tissue inhibitor of metal loproteinase-1 and a synthetic matrix metalloproteinase inhibitor. These da ta suggest that MMPs, especially MMP-2 and MMP-9, are crucial for the infil tration of inflammatory cells and the induction of airway hyperresponsivene ss, which are pathophysiologic features of bronchial asthma, and further ra ise the possibility of the inhibition of MMPs as a therapeutic strategy of bronchial asthma.