study of expression of matrix metalloproteinase-1 [MMP-1] and tissue inhibitor of metalloproteinase-1 [TIMP-1] in inflammatory bowel disease

ABSTRACT

Extracellular matrix [ECU] degradation and remodeling are major features of inflammatory bowel disease [IBD]. Matrix metalloproteinase-1 [MMP-1] is an important enzyme in ECM degradation. Its activity is controlled by tissue inhibitor ofmetalloproteinase-1 [TIMP-1]. To study the expression of MMP-1 and TIMP-1 in intestinal biopsies of patients with IBD and to determine its correlation with the endoscopic and histological scores of inflammation. Immunohistochemistry was used to study the expression of MMP-1 and TIMP-1 in 30 patients with IBD [16 patients with ulcerative colitis [UC] and 14 patients with Crohn's disease [CD]]. In addition, a control group of 10 non inflamed intestinal biopsies from these patients was studied. A semi-quantitative [ordered] method based on both the degree of staining and the percentage of positive cells was used to score immunohistochemical results. 76.67% and 90% of the studied cases of IBD showed positive staining for MMP-1 and TIMP-1 respectively. The mean staining scores of both MMP-1 and TIMP-1 were significantly higher in IBD [3.27 +/- 2 and 3.6 +/- L61 respectively] than control [0.8+0.92 and 1.9+ and .88 respectively] [p=0.001 and p-0.004 respectively]. A significant correlation was found between MMP-1 and TIMP-1 expression [p<0.001]. The expression of both MMP-1 and TIMP-1 was higher in UC [3.38 +/- 1.93 and 3.63 +/- 1.71 respectively] than CD [3.14+2.14 and 3.57 +/- 1.56 respectively], yet the difference was not significant [p=0.8 and p=0.9 respectively]. A significant correlation was detected between both MMP-1 and TIMP-1 expression and each of histological score [p<0.001] and endoscopic score [p < 0.001] of inflammation. MMP-1 and TIMP-1 are overexpressed in the affected mucosa of IBD and their expression correlates with the endoscopic and histological scores of inflammation. Thus, MMP-1 and TIMP-1 are likely to play a major role in the process of tissue destruction and remodeling in IBD. MMP-1 inhibitor therapy may prove useful in modulation of mucosal inflammation and promotion of healing in IBD