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

Imbalance of stromelysin-1 and TIMP-1 in the mucosal lesions of children with inflammatory bowel disease
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 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.
1468-3288
57-62
Heuschkel, R.B.
c2c31a22-93a2-44bc-a05a-18f416d7d508
MacDonald, T.T.
171334aa-638a-42b0-99f6-e860e2f0ca45
Monteleone, G.
bd762d44-920a-4c7d-afb3-b7a123399e73
Bajaj-Elliott, M.
811a0044-9443-4f8a-9e9d-9d8c344dc5f9
Smith, J.A.
15b087c0-3a1f-4a77-8bc7-af4194be76d3
Pender, S.L.
62528b03-ec42-41bb-80fe-48454c2c5242
Heuschkel, R.B.
c2c31a22-93a2-44bc-a05a-18f416d7d508
MacDonald, T.T.
171334aa-638a-42b0-99f6-e860e2f0ca45
Monteleone, G.
bd762d44-920a-4c7d-afb3-b7a123399e73
Bajaj-Elliott, M.
811a0044-9443-4f8a-9e9d-9d8c344dc5f9
Smith, J.A.
15b087c0-3a1f-4a77-8bc7-af4194be76d3
Pender, S.L.
62528b03-ec42-41bb-80fe-48454c2c5242

Heuschkel, R.B., MacDonald, T.T., Monteleone, G., Bajaj-Elliott, M., Smith, J.A. and Pender, S.L. (2000) Imbalance of stromelysin-1 and TIMP-1 in the mucosal lesions of children with inflammatory bowel disease. Gut, 47 (1), 57-62. (doi:10.1136/gut.47.1.57).

Record type: Article

Abstract

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.

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Published date: July 2000

Identifiers

Local EPrints ID: 73602
URI: http://eprints.soton.ac.uk/id/eprint/73602
ISSN: 1468-3288
PURE UUID: 2ae9246d-8e9c-4756-b298-f9c6bf6af97f
ORCID for S.L. Pender: ORCID iD orcid.org/0000-0001-6332-0333

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Date deposited: 10 Mar 2010
Last modified: 05 Nov 2019 01:54

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