Imbalance of stromelysin-1 and TIMP-1 in the mucosal lesions of children with inflammatory bowel disease

Background-Degradation of the extracellular matrix and ulceration of the mu cosa are major features of inflammatory bowel disease (IBD). One of the mos t important enzymes in degrading the matrix and produced in excess by cytok ine activated stromal cells, is stromelysin-1. The activity of stromelysin- 1 is controlled by tissue inhibitor of metalloproteinase (TIMP-1), its natu ral inhibitor. In model systems excess stromelysin-1 produces mucosal degra dation. Methods-Quantitative competitive RT-PCR was used to analyse stromelysin-1 a nd TIMP-1 transcripts; western blotting was used to measure the amount of s tromelysin-1 and TIMP-1 protein in biopsy samples from children with IBD. Results-In biopsies from patients with active Crohn's disease (n=24), ulcer ative colitis (n=23), and controls (n=16), TIMP-1 transcripts and protein w ere abundant and unchanged. Stromelysin-1 transcripts and protein were mark edly elevated in mucosal biopsies obtained from inflamed sites of patients with active IBD but were not elevated in adjacent endoscopically normal muc osa (n=10). Elevated levels of stromelysin-1 transcripts in active Crohn's disease (n=5) returned to normal levels following treatment with enteral nu trition. Conclusions-Stromelysin-1 is markedly overexpressed at inflamed sites in pa tients with IBD whereas TIMP-1 remains unaltered. Excess stromelysin-1 is l ikely to be responsible for loss of mucosal integrity in IBD.