Expression profiles of matrix metalloproteinases and their inhibitors in colonic inflammation related to pediatric inflammatory bowel disease

Abstract

Objective. The differential diagnosis of chronic colitis in inflammatory bowel disease (IBD) is challenging and a distinction between Crohn's disease (CD) and ulcerative colitis (UC) is not always possible. Matrix metalloproteinases (MMPs) cleave components of the extracellular matrix and their dysregulation leads to damage to the mucosa. They are involved in inflammation in IBD, as well as in eventual tissue repair. We aimed to examine putative differences in the profiles of MMPs and their tissue inhibitors [tissue inhibitors of metalloproteinase (TIMPs)] in pediatric IBD to find better tools for differential diagnosis of various IBD subgroups at the tissue level in the colon. Material and methods. Expression of MMPs -1, -7, -8, -9, -10, -12 and -26 and TIMPs -1 and -3 was studied by immunohistochemistry in colonic tissue samples of 32 pediatric patients with IBD and 11 non-IBD cases. Results. In the colon, expression of MMP-7 in epithelium was greater in CD samples compared to UC samples (1.09 versus 0.33; P = 0.010). Furthermore, epithelial MMP-10 expression was elevated in CD and UC samples compared to non-IBD samples (1.55 versus 1.00; P = 0.041 and 1.58 versus 1.00; P = 0.025, respectively). TIMP-3 expression in the stroma was higher in both the CD and UC groups when compared to non-IBD samples (2.18 versus 1.36; P = 0.026 and 2.50 versus 1.36; P = 0.002, respectively), but differences between UC and CD could not be observed. Conclusions. Increased expression of epithelial MMP-10 and stromal TIMP-3 could serve as histological indicators of IBD etiology. Epithelial MMP-7 expression, on the other hand, could help to differentiate between CD-related colitis and UC.

Key Words::

• Crohn's disease
• matrix metalloproteinase-10
• matrix metalloproteinase-7
• tissue inhibitor of metalloproteinase-3
• ulcerative colitis

Acknowledgements

We thank Professor Keichi Isaka, University of Tokyo, for MMP-26 antibodies, Ms Alli Tallqvist for skillful technical assistance and Ms. Anne Nikkonen for excellent help in collecting the patient data. This study was supported by the Academy of Finland, Finska Läkaresällskapet, Helsinki University Central Hospital Research Fund, Finnish Cultural Foundation (L. M.), Biomedicum Helsinki Foundation (L. M.), the Swedish Research Council (U. S.-K.), the Päivikki and Sakari Sohlberg Foundation (K.-L. K.) and the Finnish Pediatric Research Foundation (K.-L. K.).

Declaration of interest: There is no conflict of financial interest.