Matrix metalloproteinase levels are elevated in inflammatory bowel disease

Background & Aims: The expression of matrix metalloproteinases 1, 2, 3, and 9 was examined in biopsy specimens removed from adult and pediatric patients with ulcerative colitis and Crohn's disease. The aim of this study was to determine if the expression of these enzymes was altered between areas of actively inflamed vs. noninvolved mucosa in the same patient and between patients with diseased bowel vs. a control group of patients. Methods: Proteolytic activity was quantified by zymography using image analysis. The identity of the matrix metalloproteinases was confirmed by using inhibitors, by comparison with purified standards, and by Western immunoblotting with specific antibodies. Results: In patients with ulcerative colitis (n = 21), a significant increase (P = 0.0051) in metalloproteinase activity was found in inflamed areas of mucosa compared with noninvolved regions. The levels of activity also were significantly greater (P < 0.001) in noninvolved areas of the bowel (n = 21) compared with levels in control patients (n = 9). In Crohn's disease (n = 8), differences between ulcerated and nonulcerated sites were not significantly different but levels of protease activity at both of these sites were significantly elevated compared with levels in control patients (P < 0.03). Of the proteases detected, matrix metalloproteinase 9 was the most abundantly expressed in the inflamed bowel; neutrophils were confirmed as the likely origin of this protease. Conclusions: The abundance and activation of matrix metalloproteinases significantly increases in ulcerative colitis and Crohn's mucosa. Inhibitors of these proteolytic enzymes may therefore be of therapeutic value in the treatment of inflammatory bower disease.