PROTEASE EXPRESSION IN EXPERIMENTAL COLITIS

Extracellular matrix (ECM) is degraded by matrix metalloproteinases, c ollagenase, stromelysin and gelatinase, whose activity is strictly con trolled by tissue inhibitor of metalloproteinase (TIMP). Excessive enz yme activity could lead to tissue destruction in inflammatory bowel di sease (IBD). Using a rabbit model of chronic colitis we investigated t he temporal and spatial distribution of these enzymes by immunolocalis ation. 72 kD intracellular gelatinase was observed 3 h after initiatio n of colitis. At 6 h and 12 h, collagenase and, to a lesser extent, 72 kD and 95 kD gelatinase and stromelysin were all observed on the ECM in regions of mucosal ulceration. TIMP, however, was absent at these e arlier times suggesting uncontrolled degradation of ECM, but by 24 h, it was expressed in mucosa adjacent to areas of ulceration. At 72 h an d after one week, expression of collagenase declined and from two week s until the ulcers resolved, stromelysin and gelatinase were found at the junction of normal and ulcerated tissue. TIMP expression remained constant until ulceration had healed at 6 weeks. In colon from animals killed at 0 h, no enzyme or TIMP expression was observed. Collagenase appears to be associated with the acute phase of ulcer formation, whe reas stromelysin and gelatinase are predominant during healing.