Abstract | BACKGROUND & AIMS: METHODS: We studied mice with heterozygous disruptions in NE and PR-3, mice that express human elafin (an inhibitor of NE and PR-3), and naïve mice that received intracolonic adenoviral vectors that express elafin. Trinitrobenzene sulfonic acid (TNBS) or dextran sodium sulphate (DSS) was used to induce colitis. Protease, cytokine levels, and NF-κB activity were measured in colons of mice. Caco-2 and HT29 cells were studied in assays for cytokine expression, permeability, and NF-κB activity. RESULTS:
Elafin expression or delivery re-equilibrated the proteolytic balance in inflamed colons of mice. In mice given TNBS or DSS, transgenic expression of elafin or disruption of NE and PR-3 protected against the development of colitis. Similarly, adenoviral delivery of Elafin significantly inhibited inflammatory parameters. Elafin modulated a variety of inflammatory mediators in vitro and in vivo and strengthened intestinal epithelial barrier functions. CONCLUSIONS:
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Authors | Jean-Paul Motta, Laurent Magne, Delphyne Descamps, Corinne Rolland, Camila Squarzoni-Dale, Perrine Rousset, Laurence Martin, Nicolas Cenac, Viviane Balloy, Michel Huerre, Leopold F Fröhlich, Dieter Jenne, Julien Wartelle, Azzaq Belaaouaj, Emmanuel Mas, Jean-Pierre Vinel, Laurent Alric, Michel Chignard, Nathalie Vergnolle, Jean-Michel Sallenave |
Journal | Gastroenterology
(Gastroenterology)
Vol. 140
Issue 4
Pg. 1272-82
(Apr 2011)
ISSN: 1528-0012 [Electronic] United States |
PMID | 21199654
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Chemokines
- Cytokines
- Elafin
- NF-kappa B
- Protease Inhibitors
- Serine Proteinase Inhibitors
- Leukocyte Elastase
- Myeloblastin
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Topics |
- Adenoviridae
(genetics)
- Animals
- Caco-2 Cells
- Chemokines
(metabolism)
- Colitis
(genetics, metabolism, therapy)
- Cytokines
(metabolism)
- Elafin
(genetics, metabolism)
- Gene Expression
(physiology)
- Genetic Therapy
(methods)
- HT29 Cells
- Humans
- Leukocyte Elastase
(metabolism)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Inbred CBA
- Mice, Transgenic
- Myeloblastin
(metabolism)
- NF-kappa B
(metabolism)
- Neutrophils
(enzymology, immunology)
- Protease Inhibitors
(metabolism)
- Serine Proteinase Inhibitors
(metabolism)
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