Epithelial production of elastase is increased in inflammatory bowel disease and causes mucosal inflammation
Open accessAbstract
Imbalance between proteases and their inhibitors plays a crucial role in the development of Inflammatory Bowel Diseases (IBD). Increased elastolytic activity is observed in the colon of patients suffering from IBD. Here, we aimed at identifying the players involved in elastolytic hyperactivity associated with IBD and their contribution to the disease. We revealed that epithelial cells are a major source of elastolytic activity in healthy human colonic tissues and this activity is greatly increased in IBD patients, both in diseased and distant sites of inflammation. This study identified a previously unrevealed production of elastase 2A (ELA2A) by colonic epithelial cells, which was enhanced in IBD patients. We demonstrated that ELA2A hyperactivity is sufficient to lead to a leaky epithelial barrier. Epithelial ELA2A hyperactivity also modified the cytokine gene expression profile with an increase of pro-inflammatory cytokine transcripts, while reducing the expression of pro-resolving and repair factor genes. ELA2A thus appears as a novel actor produced by intestinal epithelial cells, which can drive inflammation and loss of barrier function, two essentials pathophysiological hallmarks of IBD. Targeting ELA2A hyperactivity should thus be considered as a potential target for IBD treatment.
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Elastase 2A is enhanced in inflammatory bowel disease patients.
“The same study specifically identified elastase 2A (ELA2A) as enhanced in IBD patients.”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [29]
Colonic epithelial cells are a major source of elastase-like activity and this activity is markedly increased in inflammatory bowel disease patients.
“Motta et al.29 showed that colonic epithelial cells are a major source of elastase-like activity and this activity is markedly increased in IBD patients.”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [29]
Host proteases such as chymase or ELA2A are able to cleave tight and adherens junction proteins including zonula occludens-1 or E-cadherin.
“Host proteases such as chymase or ELA2A are able to cleave tight and adherens junction proteins including zonula occludens-1 or E-cadherin.22,29,130”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [29]
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Ashokkumar, S., Manivasagan, P., Kalimuthu, S., Lee, Y., & Jang, E. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18111396
- Authors
- Motta, J.-P., Rolland, C., Edir, A., Florence, A.-C., Sagnat, D., Bonnart, C., Rousset, P., Guiraud, L., Quaranta-Nicaise, M., Mas, E., Bonnet, D., Verdu, E. F., McKay, D. M., Buscail, E., Alric, L., Vergnolle, N., & Deraison, C.
- Affiliations
- Université Toulouse III - Paul Sabatier (FR)
- Centre Hospitalier Universitaire de Toulouse (FR)
- McMaster University (CA)
- University of Calgary (CA)
- Corresponding author
- Vergnolle, Nathalie
- ORCID
- Venue
- Mucosal Immunology
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 14
- Issue
- 3
- Pages
- 667-678
- ISSN
- 1933-0219 (ISSN-L)
- PMC
- PMC8075934
- OpenAlex
- W3133688564
- Cited by
- 40
- References
- 47
- Citations by year
- 2026: 10 · 2025: 9 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 4
- FWCI
- 2.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Mucosal Immunology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- Funders
- Crohn's and Colitis Foundation of Canada
- European Commission (627487)
- Agence Nationale de la Recherche (ANR-12-BSV1-0030, ANR-12, ANR-11-EQPX-0003)
- Centre National de la Recherche Scientifique
- Crohn's and Colitis Canada (623780)
- FP7 Ideas: European Research Council (310973)
- CHIST-ERA
- 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
- inflammatory bowel disease, colonic epithelial cells, elastolytic activity, epithelial barrier function, mucosal inflammation, inflammatory cytokines, cytokine gene expression
- MeSH terms
- Adult, Colon, Female, Humans, Inflammation, Intestinal Mucosa, Male, Middle Aged, Inflammatory Bowel Diseases, Up-Regulation, Cytokines, Inflammation Mediators, Immunity, Mucosal, Tight Junctions, Leukocyte Elastase
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