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


METHODS
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.


RESULTS
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.


CONCLUSIONS
These findings suggest that MMP-12 may play an important role in the eosinophil infiltration of the allergic airway.
Yu
Yingyan
Y
Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Chiba
Yoshihiko
Y
Sakai
Hiroyasu
H
Misawa
Miwa
M
D000818:Animals; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004338:Drug Combinations; D004549:Elastin / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D007150:Immunohistochemistry; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D010094:Oxonic Acid / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D012130:Respiratory Hypersensitivity / Q000188:drug therapy* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D005641:Tegafur / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects
D004338:Drug Combinations; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D012313:RNA; D004549:Elastin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D020780:Matrix Metalloproteinase 9; D053508:Matrix Metalloproteinase 12