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Epithelial production of elastase is increased in inflammatory bowel disease and causes mucosal inflammation.
Motta, Jean-Paul; Rolland, Corinne; Edir, Anissa; Florence, Ana-Carolina; Sagnat, David; Bonnart, Chrystelle; Rousset, Perrine; Guiraud, Laura; Quaranta-Nicaise, Muriel; Mas, Emmanuel; Bonnet, Delphine; Verdu, Elena F; McKay, Derek M; Buscail, Etienne; Alric, Laurent; Vergnolle, Nathalie; Deraison, Céline.
Afiliación
  • Motta JP; IRSD, Université de Toulouse, INSERM, INRAe, ENVT, UPS, Toulouse, France.
  • Rolland C; IRSD, Université de Toulouse, INSERM, INRAe, ENVT, UPS, Toulouse, France.
  • Edir A; IRSD, Université de Toulouse, INSERM, INRAe, ENVT, UPS, Toulouse, France.
  • Florence AC; IRSD, Université de Toulouse, INSERM, INRAe, ENVT, UPS, Toulouse, France.
  • Sagnat D; IRSD, Université de Toulouse, INSERM, INRAe, ENVT, UPS, Toulouse, France.
  • Bonnart C; IRSD, Université de Toulouse, INSERM, INRAe, ENVT, UPS, Toulouse, France.
  • Rousset P; IRSD, Université de Toulouse, INSERM, INRAe, ENVT, UPS, Toulouse, France.
  • Guiraud L; IRSD, Université de Toulouse, INSERM, INRAe, ENVT, UPS, Toulouse, France.
  • Quaranta-Nicaise M; IRSD, Université de Toulouse, INSERM, INRAe, ENVT, UPS, Toulouse, France.
  • Mas E; IRSD, Université de Toulouse, INSERM, INRAe, ENVT, UPS, Toulouse, France.
  • Bonnet D; Unité de Gastroentérologie, Hépatologie, Nutrition, Diabétologie et Maladies Héréditaires du Métabolisme, Hôpital des Enfants, Toulouse, France.
  • Verdu EF; Pole Digestif, CHU Toulouse, Toulouse, France.
  • McKay DM; Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
  • Buscail E; Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
  • Alric L; Pole Digestif, CHU Toulouse, Toulouse, France.
  • Vergnolle N; Pole Digestif, CHU Toulouse, Toulouse, France.
  • Deraison C; IRSD, Université de Toulouse, INSERM, INRAe, ENVT, UPS, Toulouse, France. nathalie.vergnolle@inserm.fr.
Mucosal Immunol ; 14(3): 667-678, 2021 05.
Article en En | MEDLINE | ID: mdl-33674762
ABSTRACT
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.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Colon / Elastasa de Leucocito / Inflamación / Mucosa Intestinal Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Mucosal Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Enfermedades Inflamatorias del Intestino / Colon / Elastasa de Leucocito / Inflamación / Mucosa Intestinal Tipo de estudio: Etiology_studies / Prognostic_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Mucosal Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Francia