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Pàgina inicial > Articles > Articles publicats > Overexpression of corticotropin-releasing factor in intestinal mucosal eosinophils is associated with clinical severity in Diarrhea-Predominant Irritable Bowel Syndrome |
Data: | 2020 |
Resum: | Corticotropin-releasing factor (CRF) has been identified in intestinal mucosal eosinophils and associated with psychological stress and gut dysfunction. Irritable bowel syndrome (IBS) is commonly characterized by altered intestinal motility, immune activation, and increased gut barrier permeability along with heightened susceptibility to psychosocial stress. Despite intensive research, the role of mucosal eosinophils in stress-associated gut dysfunction remains uncertain. In this study, we evaluated eosinophil activation profile and CRF content in the jejunal mucosa of diarrhea-predominant IBS (IBS-D) and healthy controls (HC) by gene/protein expression and transmission electron microscopy. We also explored the association between intestinal eosinophil CRF and chronic stress, and the potential mechanisms underlying the stress response by assessing eosinophil response to neuropeptides. We found that mucosal eosinophils displayed higher degranulation profile in IBS-D as compared to HC, with increased content of CRF in the cytoplasmic granules, which significantly correlated with IBS clinical severity, life stress background and depression. Eosinophils responded to substance P and carbachol by increasing secretory activity and CRF synthesis and release, without promoting pro-inflammatory activity, a profile similar to that found in mucosal eosinophils from IBS-D. Collectively, our results suggest that intestinal mucosal eosinophils are potential contributors to stress-mediated gut dysfunction through CRF production and release. |
Ajuts: | Ministerio de Economía y Competitividad CD15/00010 Ministerio de Ciencia e Innovación CM10/00155 Instituto de Salud Carlos III PI17/01443 Ministerio de Economía y Competitividad PI15/00301 Instituto de Salud Carlos III PI17/01443 Instituto de Salud Carlos III PI19/01643 Ministerio de Economía y Competitividad CP18/00116 Instituto de Salud Carlos III CM08/00229 Ministerio de Economía y Competitividad FI12/00254 Ministerio de Educación SAF 2016-76648-R Agència de Gestió d'Ajuts Universitaris i de Recerca 2014 SGR 1285 |
Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | Irritable bowel syndrome ; Mucosal immunology |
Publicat a: | Scientific reports, Vol. 10 (november 2020) , ISSN 2045-2322 |
13 p, 1.8 MB |