Increase in the expression of matrix metalloproteinase-12 in the airways of rats with allergic bronchial asthma

Abstract

Although an involvement of matrix metalloproteinase (MMP)-12 in the development of chronic obstructive pulmonary disease (COPD) and airway inflammation has been suggested, its detailed role in the airways is not well known now. In the present study, the changes in the expression and localization of MMP-12 in airways of repeatedly antigen-challenged rats were investigated to show an association of MMP-12 with allergic bronchial asthma. Rats sensitized by dinitrophenylated Ascaris antigen were 3 times repeatedly challenged with aerosolized antigen solution to induce an asthmatic reaction. Twenty-four hours after the last antigen challenge, marked airway inflammation and bronchial smooth muscle hyperresponsiveness were observed. In this animal model of allergic bronchial asthma, a significant increase in the expression/activity of MMP-12 was found: the peak was observed at 12 h after the last antigen challenge. Furthermore, mRNA expression of MMP-12 was also increased at the early phase (1-3 h) after the last antigen challenge. Immunohistochemical studies revealed that MMP-12 was mainly expressed in airway epithelia and alveolar macrophages. These findings suggest that MMP-12 is upregulated after the induction of asthmatic reaction. MMP-12 might be a new target for the therapy against allergic bronchial asthma. © 2007 Pharmaceutical Society of Japan.