Expression of MMP-2, MMP-7, MMP-9, and TIMP-1 by Inflamed Mucosa in the Initial Diagnosis of Ulcerative Colitis as a Response Marker for Conventional Medical Treatment.

Abstract

Introduction: Experimental and clinical data involve matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs) in the pathogenesis of inflammatory bowel diseases. However, the impact of MMPs/TIMPs expression by inflamed mucosa on medical response therapy has scarcely been investigated.

Methods: The expression of MMP-2, MMP-7, MMP-9, and TIMP-1 was determined by immunohistochemical analysis in inflamed mucosa samples at diagnosis in 82 patients with ulcerative colitis (UC; 22 never-treated with corticosteroids, 28 nonresponders, and 32 responders to corticosteroid therapy) and 15 patients with acute diverticulitis (AD). The global expression (score value) of each factor was analyzed by computer-generated image analysis.

Results: UC samples showed higher MMP-2 and MMP-9 expression but lower TIMP-1 expression than the AD samples (p < 0.0001, for all). High MMP-9 and TIMP-1 scores were significantly associated with no need for corticosteroid treatment (p < 0.001 and p = 0.017, respectively); whereas higher score in the MMP-7 expression was significantly associated with nonresponse to corticosteroid therapy (p = 0.037). In addition, in this latter UC subgroup, MMP-7 correlated positively with the younger age of the patients and with the extension of the disease (p = 0.030 and p = 0.010, respectively).

Conclusion: Our results suggest the relevance of MMPs and TIMPs for predicting treatment response to both 5-aminosalicylates and corticosteroids in UC.