Effect of a matrix metalloproteinase-12 inhibitor, S-1, on allergic airway disease phenotypes in mice

Abstract

Matrix metalloproteinase-12 (MMP-12) has been reported to play an important role in chronic airway inflammatory diseases, but its detailed role in allergic airway disease is not well known. In this study, we investigated the expressions of MMP-12 and the effect of S-1, an MMP-12 inhibitor, in a mouse model of allergic airway inflammation. The expressions and activity of MMP-12 were measured by RT-PCR western blot and zymography, respectively. The locations in the airways of MMP-12 and elastin fiber were histologically studied. The mice were orally administered with S-1 during the period of antigen challenge. Bronchoalveolar lavage fluid (BALF) cells were counted, and the activity of MMP-12 in BALF was measured by zymography after the treatment with S-1. The allergen challenge model resulted in increased eosinophil number in BALF and damage to elastin fiber. Upregulation of MMP-12 was also found in the airways of challenged mice. The increased eosinophil number in the BALF after antigen challenge was inhibited by S-1. These findings suggest that MMP-12 may play an important role in the eosinophil infiltration of the allergic airway.