Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the disease

As acute pancreatitis progresses to the severe form, a life-threatening systemic inflammation is triggered. Although the mechanisms involved in this process are not yet well understood, it has been proposed that circulating exosomes may be involved in the progression of inflammation from the pancrea...

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Autores: Carrascal, Montserrat, Areny-Balagueró, Aina, Madaria, Enrique de, Cárdenas-Jaén, Karina, García-Rayado, Guillermo, Rivera, Robin, Martin Mateos, Rosa María, Pascual-Moreno, Isabel, Gironella, Meritxell, Abián, Joaquín, Closa, Daniel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/270002
Acceso en línea:http://hdl.handle.net/10261/270002
Access Level:acceso abierto
Palabra clave:Acute pancreatitis
Inflammation
Exosomes
S100A8
S100A9
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spelling Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the diseaseCarrascal, MontserratAreny-Balagueró, AinaMadaria, Enrique deCárdenas-Jaén, KarinaGarcía-Rayado, GuillermoRivera, RobinMartin Mateos, Rosa MaríaPascual-Moreno, IsabelGironella, MeritxellAbián, JoaquínClosa, DanielAcute pancreatitisInflammationExosomesS100A8S100A9As acute pancreatitis progresses to the severe form, a life-threatening systemic inflammation is triggered. Although the mechanisms involved in this process are not yet well understood, it has been proposed that circulating exosomes may be involved in the progression of inflammation from the pancreas to distant organs. Here, the inflammatory capacity and protein profile of plasma exosomes obtained during the first 24 h of hospitalization of patients diagnosed with acute pancreatitis were characterized and compared with the final severity of the disease. We found that the final severity of the disease strongly correlates with the inflammatory capacity of exosomes in the early stages of acute pancreatitis. Exosomes isolated from patients with mild pancreatitis had no effect on macrophages, while exosomes isolated from patients with severe pancreatitis triggered NFκB activation, TNFα and IL1β expression, and free radical generation. To delve deeper into the mechanism involved, we performed a proteomic analysis of the different exosomes that allowed us to identify different groups of proteins whose concentration was also correlated with the clinical classification of pancreatitis. In particular, an increase in the amount of S100A8 and S100A9 carried by exosomes of severe pancreatitis suggests that the mechanism of action of exosomes is mediated by the effect of these proteins on NADPH oxidase. This enzyme is activated by S100A8/S100A9, thus generating free radicals and promoting an inflammatory response. Along these lines, we observed that inhibition of this enzyme abolished all the pro-inflammatory effects of exosomes from severe pancreatitis. All this suggests that the systemic effects, and therefore the final severity of acute pancreatitis, are determined by the content of circulating exosomes generated in the early hours of the process. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.This work was supported by the projects PI16/00060 from Instituto de Salud Carlos III, 2019AEP057 CVSCI, and a grant ‘Gonzalo Miño’ from the Asociación Española de Gastroenterología. The Biologial and Environmental Proteomics group is a member of Proteored-PRB3 and is supported by Grant PT17/0019/0008 of the PE I+D+I 2013–2016, funded by ISCIII and FEDER.John Wiley & SonsInstituto de Salud Carlos IIIAsociación Española de GastroenterologíaEuropean CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220222022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/270002reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésCarrascal, Montserrat; Areny-Balagueró, Aina; Madaria, Enrique de; Cárdenas-Jaén, Karina; García-Rayado, Guillermo; Rivera, Robin; Martin Mateos, Rosa María; Pascual-Moreno, Isabel; Gironella, Meritxell; Abián, Joaquín; Closa, Daniel; 2022; Supporting Information Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the disease [Dataset]; John Wiley & Sons; http://dx.doi.org/10.1002/path.5811http://dx.doi.org/10.1002/path.5811Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2700022026-05-22T06:33:51Z
dc.title.none.fl_str_mv Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the disease
title Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the disease
spellingShingle Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the disease
Carrascal, Montserrat
Acute pancreatitis
Inflammation
Exosomes
S100A8
S100A9
title_short Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the disease
title_full Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the disease
title_fullStr Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the disease
title_full_unstemmed Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the disease
title_sort Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the disease
dc.creator.none.fl_str_mv Carrascal, Montserrat
Areny-Balagueró, Aina
Madaria, Enrique de
Cárdenas-Jaén, Karina
García-Rayado, Guillermo
Rivera, Robin
Martin Mateos, Rosa María
Pascual-Moreno, Isabel
Gironella, Meritxell
Abián, Joaquín
Closa, Daniel
author Carrascal, Montserrat
author_facet Carrascal, Montserrat
Areny-Balagueró, Aina
Madaria, Enrique de
Cárdenas-Jaén, Karina
García-Rayado, Guillermo
Rivera, Robin
Martin Mateos, Rosa María
Pascual-Moreno, Isabel
Gironella, Meritxell
Abián, Joaquín
Closa, Daniel
author_role author
author2 Areny-Balagueró, Aina
Madaria, Enrique de
Cárdenas-Jaén, Karina
García-Rayado, Guillermo
Rivera, Robin
Martin Mateos, Rosa María
Pascual-Moreno, Isabel
Gironella, Meritxell
Abián, Joaquín
Closa, Daniel
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Asociación Española de Gastroenterología
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Acute pancreatitis
Inflammation
Exosomes
S100A8
S100A9
topic Acute pancreatitis
Inflammation
Exosomes
S100A8
S100A9
description As acute pancreatitis progresses to the severe form, a life-threatening systemic inflammation is triggered. Although the mechanisms involved in this process are not yet well understood, it has been proposed that circulating exosomes may be involved in the progression of inflammation from the pancreas to distant organs. Here, the inflammatory capacity and protein profile of plasma exosomes obtained during the first 24 h of hospitalization of patients diagnosed with acute pancreatitis were characterized and compared with the final severity of the disease. We found that the final severity of the disease strongly correlates with the inflammatory capacity of exosomes in the early stages of acute pancreatitis. Exosomes isolated from patients with mild pancreatitis had no effect on macrophages, while exosomes isolated from patients with severe pancreatitis triggered NFκB activation, TNFα and IL1β expression, and free radical generation. To delve deeper into the mechanism involved, we performed a proteomic analysis of the different exosomes that allowed us to identify different groups of proteins whose concentration was also correlated with the clinical classification of pancreatitis. In particular, an increase in the amount of S100A8 and S100A9 carried by exosomes of severe pancreatitis suggests that the mechanism of action of exosomes is mediated by the effect of these proteins on NADPH oxidase. This enzyme is activated by S100A8/S100A9, thus generating free radicals and promoting an inflammatory response. Along these lines, we observed that inhibition of this enzyme abolished all the pro-inflammatory effects of exosomes from severe pancreatitis. All this suggests that the systemic effects, and therefore the final severity of acute pancreatitis, are determined by the content of circulating exosomes generated in the early hours of the process. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/270002
url http://hdl.handle.net/10261/270002
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Carrascal, Montserrat; Areny-Balagueró, Aina; Madaria, Enrique de; Cárdenas-Jaén, Karina; García-Rayado, Guillermo; Rivera, Robin; Martin Mateos, Rosa María; Pascual-Moreno, Isabel; Gironella, Meritxell; Abián, Joaquín; Closa, Daniel; 2022; Supporting Information Inflammatory capacity of exosomes released in the early stages of acute pancreatitis predicts the severity of the disease [Dataset]; John Wiley & Sons; http://dx.doi.org/10.1002/path.5811
http://dx.doi.org/10.1002/path.5811
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv John Wiley & Sons
publisher.none.fl_str_mv John Wiley & Sons
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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