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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Motta, JP; Magne, L; Descamps, D; Rolland, C; Squarzoni-Dale, C; Rousset, P; Martin, L; Cenac, N; Balloy, V; Huerre, M; Fröhlich, LF; Jenne, D; Wartelle, J; Belaaouaj, A; Mas, E; Vinel, JP; Alric, L; Chignard, M; Vergnolle, N; Sallenave, JM.
Modifying the protease, antiprotease pattern by elafin overexpression protects mice from colitis.
Gastroenterology. 2011; 140(4): 1272-1282.
Doi: 10.1053/j.gastro.2010.12.050
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Fröhlich Leopold F.
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- Abstract:
- BACKGROUND & AIMS: Colonic tissues of patients with inflammatory bowel disease have been reported to have increased proteolytic activity, but no studies have clearly addressed the role of the balance between proteases and antiproteases in the pathogenesis of colitis. We investigated the role of Elafin, a serine protease inhibitor expressed by skin and mucosal surfaces in human inflammatory conditions, and the proteases neutrophil elastase (NE) and proteinase-3 (PR-3) in mice with colitis. 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 naive 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-kappa B activity were measured in colons of mice. Caco-2 and HT29 cells were studied in assays for cytokine expression, permeability, and NF-kappa B 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: The protease inhibitor Elafin prevents intestinal inflammation in mouse models of colitis and might be developed as a therapeutic agent for inflammatory bowel disease.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenoviridae - genetics
- Animals -
- Caco-2 Cells -
- Chemokines - metabolism
- Colitis - genetics
- Cytokines - metabolism
- Elafin - genetics
- Gene Expression - physiology
- Gene 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
- Protease Inhibitors - metabolism
- Serine Proteinase Inhibitors - metabolism
- Find related publications in this database (Keywords)
- Crohn's Disease
- Ulcerative Colitis
- Protein Degradation
- Proteolysis