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

被引:124
作者
Heuschkel, RB
MacDonald, TT
Monteleone, G
Bajaj-Elliott, M
Smith, JAW
Pender, SLF
机构
[1] UCL Royal Free & Univ Coll Med Sch, Dept Pediat Gastroenterol, London, England
[2] St Bartholomews & Royal London Sch Med & Dent, Dept Paediat Gastroenterol, London, England
关键词
inflammatory bowel disease; enteral nutrition; intestine; matrix metalloproteinase; tissue inhibitor of metalloproteinase;
D O I
10.1136/gut.47.1.57
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:57 / 62
页数:6
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