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Suppression of T cell-mediated injury in human gut by interleukin 10: role of matrix metalloproteinases

Suppression of T cell-mediated injury in human gut by interleukin 10: role of matrix metalloproteinases
Suppression of T cell-mediated injury in human gut by interleukin 10: role of matrix metalloproteinases
BACKGROUND & AIMS: Activation of lamina propria T cells with pokeweed mitogen in human fetal gut explant cultures results in severe mucosal injury. In the same system, Staphylococcus aureus enterotoxin B produces villus atrophy and crypt cell hyperplasia. The aim of this study was to examine the ability of interleukin (IL)-10 to modify these changes. METHODS: Mucosal pathology and lamina propria glycosaminoglycans were assessed histologically, and CD3(+), CD25(+) and alpha-actin smooth muscle-positive cells were determined by immunohistochemistry. Reverse plaque assays and quantitative reverse-transcriptase polymerase chain reaction were used to analyze the cytokine response. Matrix metalloproteinase production was analyzed by Western blotting, in situ hybridization, and zymography. RESULTS: Both experimental enteropathies produced mucosal damage, although injury was greater after pokeweed mitogen activation than S. aureus enterotoxin B. In both cases, the increase in cytokine-secreting cells and transcripts observed after T-cell activation was inhibited by IL-10. IL-10 also inhibited the increase in collagenase and stromelysin-1 in the explant culture supernatants and the loss of glycosaminoglycans. IL-10 decreased metalloproteinase production in control explants and increased matrix. In mesenchymal cells, IL-10 had a minor effect on metalloproteinase production. CONCLUSIONS: IL-10 down-regulates mucosal T-cell activation, metalloproteinase production, and loss of extracellular matrix and prevents mucosal damage in the gut.
0016-5085
573-583
Pender, SL
62528b03-ec42-41bb-80fe-48454c2c5242
Breese, E.J.
03949ac9-84f7-4bf4-9e60-8c1c4fed4fbe
Gunther, U.
c5621df2-4fa8-4357-8934-25c37c653f96
Howie, D.
9efdee45-a03d-49d0-b738-27e960286bd0
Wathen, N.C.
ed64bb03-0dc2-4b8c-b5d5-8a1ee4ed902b
Schuppan, D.
09ab1e29-a176-43d9-876e-7e95563a21b6
MacDonald, T.T.
171334aa-638a-42b0-99f6-e860e2f0ca45
Pender, SL
62528b03-ec42-41bb-80fe-48454c2c5242
Breese, E.J.
03949ac9-84f7-4bf4-9e60-8c1c4fed4fbe
Gunther, U.
c5621df2-4fa8-4357-8934-25c37c653f96
Howie, D.
9efdee45-a03d-49d0-b738-27e960286bd0
Wathen, N.C.
ed64bb03-0dc2-4b8c-b5d5-8a1ee4ed902b
Schuppan, D.
09ab1e29-a176-43d9-876e-7e95563a21b6
MacDonald, T.T.
171334aa-638a-42b0-99f6-e860e2f0ca45

Pender, SL, Breese, E.J., Gunther, U., Howie, D., Wathen, N.C., Schuppan, D. and MacDonald, T.T. (1998) Suppression of T cell-mediated injury in human gut by interleukin 10: role of matrix metalloproteinases. Gastroenterology, 115 (3), 573-583. (doi:10.1016/S0016-5085(98)70136-2).

Record type: Article

Abstract

BACKGROUND & AIMS: Activation of lamina propria T cells with pokeweed mitogen in human fetal gut explant cultures results in severe mucosal injury. In the same system, Staphylococcus aureus enterotoxin B produces villus atrophy and crypt cell hyperplasia. The aim of this study was to examine the ability of interleukin (IL)-10 to modify these changes. METHODS: Mucosal pathology and lamina propria glycosaminoglycans were assessed histologically, and CD3(+), CD25(+) and alpha-actin smooth muscle-positive cells were determined by immunohistochemistry. Reverse plaque assays and quantitative reverse-transcriptase polymerase chain reaction were used to analyze the cytokine response. Matrix metalloproteinase production was analyzed by Western blotting, in situ hybridization, and zymography. RESULTS: Both experimental enteropathies produced mucosal damage, although injury was greater after pokeweed mitogen activation than S. aureus enterotoxin B. In both cases, the increase in cytokine-secreting cells and transcripts observed after T-cell activation was inhibited by IL-10. IL-10 also inhibited the increase in collagenase and stromelysin-1 in the explant culture supernatants and the loss of glycosaminoglycans. IL-10 decreased metalloproteinase production in control explants and increased matrix. In mesenchymal cells, IL-10 had a minor effect on metalloproteinase production. CONCLUSIONS: IL-10 down-regulates mucosal T-cell activation, metalloproteinase production, and loss of extracellular matrix and prevents mucosal damage in the gut.

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Published date: September 1998

Identifiers

Local EPrints ID: 76233
URI: http://eprints.soton.ac.uk/id/eprint/76233
ISSN: 0016-5085
PURE UUID: ca382d69-3371-4d8f-b05d-8bca538253ac
ORCID for SL Pender: ORCID iD orcid.org/0000-0001-6332-0333

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Date deposited: 11 Mar 2010
Last modified: 14 Mar 2024 02:45

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Contributors

Author: SL Pender ORCID iD
Author: E.J. Breese
Author: U. Gunther
Author: D. Howie
Author: N.C. Wathen
Author: D. Schuppan
Author: T.T. MacDonald

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