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Cited by 130Inflammatory Bowel DiseaseProtease and Inhibitor MechanismsAutoimmune and Inflammatory Disorders

Modifying the Protease, Antiprotease Pattern by Elafin Overexpression Protects Mice From Colitis

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Motta, Jean–Paul, Magne, Laurent, Descamps, Delphyne, Rolland, Corinne, Squarzoni–Dale, Camila, Rousset, Perrine, Martin, Laurence, Cenac, Nicolas +12 more·2011·Gastroenterology
DOI 10.1053/j.gastro.2010.12.050
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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 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 The protease inhibitor Elafin prevents intestinal inflammation in mouse models of colitis and might be developed as a therapeutic agent for inflammatory bowel disease.

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  • Inhibitors of serine proteases have beneficial effects in mouse models of inflammatory bowel disease.

    “Consistent with a role of proteolytic overactivity in disease pathogenesis, inhibitors of serine proteases have beneficial effects in mouse models of IBD.27,30”

    From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [30]

  • Elafin, a Lactobacillus-derived inhibitor of serine proteases, reduces the severity of colitis in mice exposed to dextran sulfate sodium or trinitro benzene sulphonic acid.

    “Elafin, a Lactobacillus-derived inhibitor of serine proteases reduced the severity of colitis in mice exposed to dextran sulfate sodium (DSS) or trinitro benzene sulphonic acid.27,30,31”

    From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [30]

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Authors
Motta, J., Magne, L., Descamps, D., Rolland, C., Squarzoni–Dale, C., Rousset, P., Martin, L., Cenac, N., Balloy, V., Huerre, M., Fröhlich, L. F., Jenne, D., Wartelle, J., Belaaouaj, A., Mas, E., Vinel, J., Alric, L., Chignard, M., Vergnolle, N., & Sallenave, J.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Inserm (FR)
  • Institut Pasteur (FR)
  • Medical University of Graz (AT)
  • Max Planck Institute of Neurobiology (DE)
  • Centre Hospitalier Universitaire de Reims (FR)
Corresponding author
Vergnolle, Nathalie
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2011-04
Volume
140
Issue
4
Pages
1272-1282
ISSN
0016-5085 (ISSN-L)
DOI
10.1053/j.gastro.2010.12.050
OpenAlex
W2034056147
Cited by
130
References
33
Citations by year
2026: 5 · 2025: 12 · 2024: 8 · 2023: 3 · 2022: 11 · 2021: 16 · 2020: 11 · 2019: 7 · 2018: 4 · 2017: 9 · 2016: 7 · 2015: 7 · 2014: 11 · 2013: 7 · 2012: 7
FWCI
5.99
Type
journal article
Language
en
Open access
Licence
Locations
  • Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • HAL (submittedVersion, other-oa)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Max Planck Digital Library (submittedVersion)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
  • Health Sciences › Medicine › Epidemiology › Autoimmune and Inflammatory Disorders
Keywords
elafin, colitis, inflammatory bowel disease, neutrophil elastase, proteinase 3, serine protease inhibitors, protease-antiprotease balance, TNBS-induced colitis, DSS-induced colitis, NF-κB, intestinal epithelial barrier, adenoviral gene transfer, cytokine expression, intestinal permeability
MeSH terms
Adenoviridae, Animals, Colitis, Humans, Male, Mice, Inbred CBA, Mice, Inbred C57BL, Mice, Transgenic, Neutrophils, Protease Inhibitors, Genetic Therapy, Serine Proteinase Inhibitors, Gene Expression, Cytokines, NF-kappa B, Chemokines, Caco-2 Cells, HT29 Cells, Leukocyte Elastase, Mice, Myeloblastin, Elafin

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