Protease Activity in a Hapten-Induced Model of Ulcerative Colitis in Rats

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James V. Hawkins
Eva L. Emmel
Jennifer J. Feuer
Mark A. Nedelman
Catherine J. Harvey
Hilton J. Klein
Harry Rozmiarek
Ann R. Kennedy
Gary R. Lichtenstein
Paul C. Billings
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PROTEASE ACTIVITY; ULCERATIVE COLITIS;
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Inflammatory bowel disease (IBD) is a painfuland debilitating condition affecting the mucosal liningof the colon and other areas of the gastrointestinaltract. IBD generally falls into two major categories: ulcerative colitis (UC) and Crohn's disease. Wehave utilized dinitrobenzenesulfonic acid (DNBS) toinduce experimental UC in rats. Histopathologic analysisindicates that DNBS induces a condition in animals similar to human UC. Biochemical resultsrevealed 6- to 10-fold elevated levels of serineprotease activity in colon tissue from animals with UCas compared with matched controls. We also observedelevated levels of protease activity in tissue samplesobtained from human patients with UC. Hence, our resultsdemonstrate that protease activity is increased inrodent and human UC. These proteases may play a significant role in destruction of colonictissue in IBD. Protease inhibitors that target serineproteases may be useful pharmacological agents to limittissue destruction in IBD.
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页码:1969 / 1980
页数:11
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