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

• Published in: Gut 2000-07, Vol.47 (1), p.57-62
• Main Authors: Heuschkel, R B, MacDonald, T T, Monteleone, G, Bajaj-Elliott, M, Smith, J A Walker, Pender, S L F
• Format: Article
• Language: English
• Subjects: Arthritis; Binding sites; Biological and medical sciences; Biopsy; Blotting, Western; Child; Colitis, Ulcerative - enzymology; Colitis, Ulcerative - metabolism; Colleges & universities; Colon; Crohn Disease - enzymology; Crohn Disease - metabolism; Crohn's disease; Cytokines; Endoscopy; Enteral Nutrition; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Inflammation; Inflammatory bowel disease; Inflammatory Bowel Diseases - enzymology; Inflammatory Bowel Diseases - metabolism; Inflammatory Bowel Diseases - therapy; Intestinal Mucosa - enzymology; Intestinal Mucosa - metabolism; intestine; matrix metalloproteinase; Matrix Metalloproteinase 3 - genetics; Matrix Metalloproteinase 3 - metabolism; Medical sciences; Nutrition; Other diseases. Semiology; Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Rodents; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; tissue inhibitor of metalloproteinase; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Transcription, Genetic
• ISSN: 0017-5749; 1468-3288; 1458-3288
• DOI: 10.1136/gut.47.1.57

BACKGROUND Degradation of the extracellular matrix and ulceration of the mucosa are major features of inflammatory bowel disease (IBD). One of the most important enzymes in degrading the matrix and produced in excess by cytokine activated stromal cells, is stromelysin-1. The activity of stromelysin-1 is controlled by tissue inhibitor of metalloproteinase (TIMP-1), its natural inhibitor. In model systems excess stromelysin-1 produces mucosal degradation. METHODS Quantitative competitive RT-PCR was used to analyse stromelysin-1 and TIMP-1 transcripts; western blotting was used to measure the amount of stromelysin-1 and TIMP-1 protein in biopsy samples from children with IBD. RESULTS In biopsies from patients with active Crohn's disease (n=24), ulcerative colitis (n=23), and controls (n=16), TIMP-1 transcripts and protein were abundant and unchanged. Stromelysin-1 transcripts and protein were markedly elevated in mucosal biopsies obtained from inflamed sites of patients with active IBD but were not elevated in adjacent endoscopically normal mucosa (n=10). Elevated levels of stromelysin-1 transcripts in active Crohn's disease (n=5) returned to normal levels following treatment with enteral nutrition. CONCLUSIONS Stromelysin-1 is markedly overexpressed at inflamed sites in patients with IBD whereas TIMP-1 remains unaltered. Excess stromelysin-1 is likely to be responsible for loss of mucosal integrity in IBD.