Effect of a matrix metalloproteinase-12 inhibitor, S-1, on allergic airway disease phenotypes in mice
Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. Agents and Actions
(Impact Factor: 2.35).
06/2010; 59(6):419-28. DOI: 10.1007/s00011-009-0153-0
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.
Available from: Nicholas G Kounis
- "Other experiments have shown that allergen challenge in mice has resulted in eosinophil increase in bronchoalveolar lavage fluid, upregulation of matrix metalloproteinase-12 and damage to elastin fibers . "
Available from: Roosmarijn E Vandenbroucke
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ABSTRACT: In the present study, we tried to develop a mouse model of chronic airway inflammation and remodeling induced by chronic exposure to antigen. Furthermore, the expressions of MMPs-9 and -12 were also investigated. BALB/c mice were sensitized and then repeatedly challenged with OVA every 3 days for 54 days. At the following day after the last challenge, of days 24, 39, and 54, histological changes of the airways were studied by hematoxylin-eosin and Masson's trichrome stains. The expressions of MMPs-9 and -12 were also measured by western blot. Persistent inflammatory cells infiltration and collagen deposition in the lung tissue were observed in repeatedly challenged mice. Furthermore, the expressions of MMPs-9 and -12 were increased in the airways after repeated antigen challenges. The severest inflammation was observed in the day-54 challenged group. These results suggest that MMPs-9 and -12 might be involved in the pathogenesis of chronic airway inflammation and remodeling induced by antigen exposure in mice.
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