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          Institute: MPI für Neurobiologie     Collection: Neuroimmunology     Display Documents



  history
ID: 562572.0, MPI für Neurobiologie / Neuroimmunology
Modifying the Protease, Antiprotease Pattern by Elafin Overexpression Protects Mice From Colitis
Authors:Motta, J. P.; Magne, L.; Descamps, D.; Rolland, C.; Squarzoni-Dale, C.; Rousset, P.; Martin, L.; Cenac, N.; Balloy, V.; Huerre, M.; Frohlich, L. F.; Jenne, D.; Wartelle, J.; Belaaouaj, A.; Mas, E.; Vinel, J. P.; Alric, L.; Chignard, M.; Vergnolle, N.; Sallenave, J. M.
Language:English
Date of Publication (YYYY-MM-DD):2011-04
Title of Journal:Gastroenterology
Journal Abbrev.:Gastroenterology
Volume:140
Issue / Number:4
Start Page:1272
End Page:1282
Review Status:Peer-review
Audience:Not Specified
Abstract / Description: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.
Free Keywords:Crohn's Disease; Ulcerative Colitis; Protein Degradation; Proteolysis
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Affiliations:MPI für Neurobiologie/Neuroimmunology (Wekerle)
External Affiliations:[Motta, Jean-Paul; Rolland, Corinne; Squarzoni-Dale, Camila; Rousset, Perrine; Martin, Laurence; Cenac, Nicolas; Mas, Emmanuel; Vinel, Jean-Pierre; Alric, Laurent; Vergnolle, Nathalie] INSERM, U1043, F-31300 Toulouse, France.; [Motta, Jean-Paul; Rolland, Corinne; Squarzoni-Dale, Camila; Rousset, Perrine; Martin, Laurence; Cenac, Nicolas; Vergnolle, Nathalie] CNRS, U5282, F-31300 Toulouse, France.; [Motta, Jean-Paul; Rolland, Corinne; Squarzoni-Dale, Camila; Rousset, Perrine; Martin, Laurence; Cenac, Nicolas; Mas, Emmanuel; Vinel, Jean-Pierre; Alric, Laurent; Vergnolle, Nathalie; Sallenave, Jean-Michel] Univ Toulouse, UPS, CPTP, Toulouse, France.; [Magne, Laurent; Descamps, Delphyne; Balloy, Viviane; Chignard, Michel; Sallenave, Jean-Michel] Inst Pasteur, Unite Def Innee & Inflammat, Paris, France.; INSERM, U874, Paris, France.; [Magne, Laurent; Descamps, Delphyne; Balloy, Viviane; Chignard, Michel; Sallenave, Jean-Michel] Univ Paris Diderot, UFR Sci Vivant, Paris, France.; [Magne, Laurent; Huerre, Michel; Sallenave, Jean-Michel] Inst Pasteur, Unite Rech & Expertise Histotechnol & Pathol, Paris, France.; [Wartelle, Julien; Belaaouaj, Azzaq] CHU Reims, EA 4303, Reims, France.; [Froehlich, Leopold F.] Med Univ Graz, Inst Pathol, Graz, Austria.
Identifiers:ISI:000288789900034 [ID No:1]
ISSN:0016-5085 [ID No:2]
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