1. Epithelial production of elastase is increased in inflammatory bowel disease and causes mucosal inflammation
- Author
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Perrine Rousset, Laurent Alric, Anissa Edir, Chrystelle Bonnart, Jean-Paul Motta, Céline Deraison, David Sagnat, Elena F. Verdu, Derek M. McKay, Corinne Rolland, Emmanuel Mas, Laura Guiraud, Delphine Bonnet, Nathalie Vergnolle, Muriel Quaranta-Nicaise, Etienne Buscail, Ana Carolina Rodrigues Florence, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Toulouse [Toulouse], McMaster University [Hamilton, Ontario], University of Calgary, ANR JCJC-11JSV1 001 01, AOL-MICILIP project, ANR-12-BSV1-0030,ELAPROB-IBD,Mecanismes d'action des probiotiques recombinants pour l'Elafine: Leur utilisation possible pour traiter les maladies inflammatoires chroniques de l'intestin?(2012), ANR-11-EQPX-0003,ANINFIMIP,Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées(2011), European Project: 627487,EC:FP7:PEOPLE,FP7-PEOPLE-2013-IOF,EPIMACASE(2014), European Project: 310973,EC:FP7:ERC,ERC-2012-StG_20111109,PIPE(2013), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), SEGUIN, Nathalie, BLANC - Mecanismes d'action des probiotiques recombinants pour l'Elafine: Leur utilisation possible pour traiter les maladies inflammatoires chroniques de l'intestin? - - ELAPROB-IBD2012 - ANR-12-BSV1-0030 - BLANC - VALID, Equipements plateforme animalerie infectieuse de haute-sécurité de Midi Pyrénées - - ANINFIMIP2011 - ANR-11-EQPX-0003 - EQPX - VALID, THE ROLE OF ELASTASE/ELASTASE INHIBITOR IN DIALOG BETWEEN INTESTINAL EPITHELIAL CELLS AND MACROPHAGES IN INFLAMMATORY BOWEL DISEASES CONTEXT - EPIMACASE - - EC:FP7:PEOPLE2014-08-06 - 2016-08-05 - 627487 - VALID, and Physiology of the Intestine: Proteases from the Epithelium - PIPE - - EC:FP7:ERC2013-04-01 - 2018-03-31 - 310973 - VALID
- Subjects
0301 basic medicine ,Adult ,Male ,Proteases ,[SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Colon ,medicine.medical_treatment ,Immunology ,Inflammation ,Disease ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Inflammatory bowel disease ,Article ,Tight Junctions ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Immunology and Allergy ,Medicine ,Humans ,Intestinal Mucosa ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Immunity, Mucosal ,Barrier function ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,business.industry ,Elastase ,Middle Aged ,medicine.disease ,Inflammatory Bowel Diseases ,Pathophysiology ,digestive system diseases ,3. Good health ,Up-Regulation ,030104 developmental biology ,Cytokine ,Cytokines ,030211 gastroenterology & hepatology ,Female ,medicine.symptom ,Inflammation Mediators ,business ,Leukocyte Elastase ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; 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.
- Published
- 2021