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

Overview

Journal Dig Dis Sci

Specialty Gastroenterology

Date 1997 Oct 23

PMID 9331164

Citations 18

Authors

J V Hawkins

E L Emmel

J J Feuer

M A Nedelman

C J Harvey

H J Klein

H Rozmiarek

A R Kennedy

G R Lichtenstein

P C Billings

Affiliations

Soon will be listed here.

Abstract

Inflammatory bowel disease (IBD) is a painful and debilitating condition affecting the mucosal lining of the colon and other areas of the gastrointestinal tract. IBD generally falls into two major categories: ulcerative colitis (UC) and Crohn's disease. We have utilized dinitrobenzenesulfonic acid (DNBS) to induce experimental UC in rats. Histopathologic analysis indicates that DNBS induces a condition in animals similar to human UC. Biochemical results revealed 6- to 10-fold elevated levels of serine protease activity in colon tissue from animals with UC as compared with matched controls. We also observed elevated levels of protease activity in tissue samples obtained from human patients with UC. Hence, our results demonstrate that protease activity is increased in rodent and human UC. These proteases may play a significant role in destruction of colonic tissue in IBD. Protease inhibitors that target serine proteases may be useful pharmacological agents to limit tissue destruction in IBD.

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References

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Billings P, Newberne P, Kennedy A . Protease inhibitor suppression of colon and anal gland carcinogenesis induced by dimethylhydrazine. Carcinogenesis. 1990; 11(7):1083-6. DOI: 10.1093/carcin/11.7.1083. View

Bohe M . Pancreatic and granulocytic endoproteases in faecal extracts from patients with active ulcerative colitis. Scand J Gastroenterol. 1987; 22(1):59-64. DOI: 10.3109/00365528708991857. View

Bohe M, GENELL S, Ohlsson K . Protease inhibitors in plasma and faecal extracts from patients with active inflammatory bowel disease. Scand J Gastroenterol. 1986; 21(5):598-604. DOI: 10.3109/00365528609003106. View

Krawisz J, Sharon P, Stenson W . Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Assessment of inflammation in rat and hamster models. Gastroenterology. 1984; 87(6):1344-50. View

Tikhonova T, Larionova N, Gladysheva I, Kazanskaia N . [Bowman-Birk soy inhibitor as an affinity ligand for isolating leukocyte elastase. Inhibition of elastin hydrolysis, catalyzed by leukocyte elastase]. Biokhimiia. 1993; 58(11):1669-76. View

Playford R, Hanby A, Patel K, Calam J . Influence of inflammatory bowel disease on the distribution and concentration of pancreatic secretory trypsin inhibitor within the colon. Am J Pathol. 1995; 146(2):310-6. PMC: 1869860. View

Nahas F, LESKOWITZ S . The ability of hapten-conjugated cells to induce cell-mediated cytotoxicity is affected by the mode of hapten linkage. Cell Immunol. 1980; 54(1):241-7. DOI: 10.1016/0008-8749(80)90205-1. View

Billings P, Habres J . A growth-regulated protease activity that is inhibited by the anticarcinogenic Bowman-Birk protease inhibitor. Proc Natl Acad Sci U S A. 1992; 89(7):3120-4. PMC: 48816. DOI: 10.1073/pnas.89.7.3120. View

10.

Brynskov J, Nielsen O, Ahnfelt-Ronne I, Bendtzen K . Cytokines (immunoinflammatory hormones) and their natural regulation in inflammatory bowel disease (Crohn's disease and ulcerative colitis): a review. Dig Dis. 1994; 12(5):290-304. DOI: 10.1159/000171464. View

11.

Rudolph U, Finegold M, Rich S, Harriman G, Srinivasan Y, Brabet P . Ulcerative colitis and adenocarcinoma of the colon in G alpha i2-deficient mice. Nat Genet. 1995; 10(2):143-50. DOI: 10.1038/ng0695-143. View

12.

Wallace J, Keenan C . An orally active inhibitor of leukotriene synthesis accelerates healing in a rat model of colitis. Am J Physiol. 1990; 258(4 Pt 1):G527-34. DOI: 10.1152/ajpgi.1990.258.4.G527. View

13.

Moy L, Billings P . A proteolytic activity in a human breast cancer cell line which is inhibited by the anticarcinogenic Bowman-Birk protease inhibitor. Cancer Lett. 1994; 85(2):205-10. DOI: 10.1016/0304-3835(94)90276-3. View

14.

Podolsky D . Inflammatory bowel disease (1). N Engl J Med. 1991; 325(13):928-37. DOI: 10.1056/NEJM199109263251306. View

15.

Larionova N, Gladysheva I, Tikhonova T, Kazanskaia N . [Inhibition of cathepsin G and elastase from human granulocytes by multiple forms of the Bowman-Birk type of soy inhibitor]. Biokhimiia. 1993; 58(9):1437-44. View

16.

Ottonello L, Dapino P, Pastorino G, Vitale E, Dallegri F . The drug 5-aminosalicylic acid rescues alpha 1-proteinase inhibitor from the neutrophil oxidative inactivation. A possible contribution to its therapeutic action in ulcerative colitis. Digestion. 1992; 51(3):140-5. DOI: 10.1159/000200889. View

17.

Billings P, Habres J, Liao D, Tuttle S . Human fibroblasts contain a proteolytic activity which is inhibited by the Bowman-Birk protease inhibitor. Cancer Res. 1991; 51(20):5539-43. View

18.

Senda S, Fujiyama Y, Bamba T, Hosoda S . Treatment of ulcerative colitis with camostat mesilate, a serine protease inhibitor. Intern Med. 1993; 32(4):350-4. DOI: 10.2169/internalmedicine.32.350. View

19.

Weiss S . Tissue destruction by neutrophils. N Engl J Med. 1989; 320(6):365-76. DOI: 10.1056/NEJM198902093200606. View

20.

Morris G, Beck P, Herridge M, Depew W, Szewczuk M, Wallace J . Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology. 1989; 96(3):795-803. View