The Impact of Matrix Metalloproteinases and Their Tissue Inhibitors in Inflammatory Bowel Diseases

Background: It has been suggested that matrix metalloproteinases (MMPs) may play a role in the pathogenesis of inflammatory bowel diseases (IBD). However, the impact of serum MMPs and their inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] have scarcely been investigated in the same experimental setting in ulcerative colitis (UC) and Crohn’s disease (CD) as well as their correlation with IBD activity. Methods: MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 serum antigen levels were determined in 23 patients with UC, 25 patients with CD and 10 healthy control patients by enzyme-linked immunoassay technique. Statistical analysis with one-way ANOVA and Student’s t tests was performed. A linear regression analysis or a Spearman’s r test was used to assess correlation. Differences were considered significant with p < 0.05. Results: Serum antigen concentrations of MMP-9, TIMP-1 and TIMP-2 were significantly higher in UC and CD patients compared to controls. MMP-7 was also significantly higher in CD compared with controls. Elevated MMP-9 and TIMP-1 antigen levels showed significant positive correlation with disease activity of IBD. MMP-2 and TIMP-2 levels inversely correlated with CD activity. Significant correlations were found between MMP-9/TIMP-1 and MMP-2/TIMP-2 antigen levels in both UC and CD. Conclusions: We demonstrated that serum antigen concentrations of MMP-9, TIMP-1 and TIMP-2 were significantly increased in patients with UC and CD compared to controls. Our results suggest that MMPs and TIMPs may contribute to the inflammatory and remodeling processes in IBD. Serum MMP-9 and TIMP-1 might be useful as additional biomarkers in the assessment of IBD activity.

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