Matrix metalloproteinase (MMP)-9 plays an important role in the pathogenesis of
colitis. Recent studies have demonstrated that
chymase is involved in the conversion of promatrix
metalloproteinase (proMMP)-9 to MMP-9. However, whether
chymase contributes to the activation of
proMMP-9 in
colitis has remained unclear. In this study, we administered 5%
dextran sodium sulfate (DSS)
solution to mice for 7 days. At 7 days after starting administration, both
chymase activity and MMP-9 activity were significantly increased. In extract from
colitis in DSS-treated mice, MMP-9 activity was significantly increased after 8 h of incubation, but increased activity was almost completely suppressed in the presence of a
chymase inhibitor, 2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidine-1-yl)-N-[{3,4-dioxo-1-phenyl-7-(2-pyridyloxy)}-2-heptyl]
acetamide (
NK3201). At 7 days after starting administration, intestinal length was significantly shorter in DSS-treated mice than in normal mice, but these changes were significantly prevented by
NK3201 (10 mg/kg per day i.p.). Disease activity index and histological damage score were also significantly reduced by
NK3201. The filtrated neutrophil number was significantly decreased by
NK3201. Furthermore,
NK3201 significantly attenuated not only
chymase activity but also MMP-9 activity in DSS-treated mice. These findings suggest that
chymase plays an important role in the development of
colitis via MMP-9 activation.