Extracellular matrix (ECM) is degraded by matrix metalloproteinases, collagenase, stromelysin and gelatinase, whose activity is strictly controlled by tissue inhibitor of metalloproteinase (TIMP). Excessive enzyme activity could lead to tissue destruction in inflammatory bowel disease (IBD). Using a rabbit model of chronic colitis we investigated the temporal and spatial distribution of these enzymes by immunolocalisation. 72 kD intracellular gelatinase was observed 3 h after initiation 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 earlier times suggesting uncontrolled degradation of ECM, but by 24 h, it was expressed in mucosa adjacent to areas of ulceration. At 72 h and after one week, expression of collagenase declined and from two weeks 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, whereas stromelysin and gelatinase are predominant during healing.
