SUCNR1 Mediates the Priming Step of the Inflammasome in Intestinal Epithelial Cells: Relevance in Ulcerative Colitis.

Intestinal epithelial cells (IECs) constitute a defensive physical barrier in mucosal tissues and their disruption is involved in the etiopathogenesis of several inflammatory pathologies, such as Ulcerative Colitis (UC). Recently, the succinate receptor SUCNR1 was associated with the activation of i...

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Autores: Bauset, C, Lis-Lopez, L, Coll, S, Gisbert-Ferrandiz, L, Macias-Ceja, DC, Seco-Cervera, M, Navarro, F, Esplugues, JV, Calatayud, S, Ortiz-Masia, D, Barrachina, MD, Cosin-Roger, J
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2022
País:España
Recursos:INCLIVA
Repositório:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
OAI Identifier:oai:incliva.fundanetsuite.com:p16656
Acesso em linha:https://incliva.portalinvestigacion.com/publicaciones/16656
Access Level:Acceso aberto
Palavra-chave:SUCNR1
Ulcerative Colitis
epithelial cells
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spelling SUCNR1 Mediates the Priming Step of the Inflammasome in Intestinal Epithelial Cells: Relevance in Ulcerative Colitis.Bauset, CLis-Lopez, LColl, SGisbert-Ferrandiz, LMacias-Ceja, DCSeco-Cervera, MNavarro, FEsplugues, JVCalatayud, SOrtiz-Masia, DBarrachina, MDCosin-Roger, JSUCNR1Ulcerative Colitisepithelial cellsIntestinal epithelial cells (IECs) constitute a defensive physical barrier in mucosal tissues and their disruption is involved in the etiopathogenesis of several inflammatory pathologies, such as Ulcerative Colitis (UC). Recently, the succinate receptor SUCNR1 was associated with the activation of inflammatory pathways in several cell types, but little is known about its role in IECs. We aimed to analyze the role of SUCNR1 in the inflammasome priming and its relevance in UC. Inflammatory and inflammasome markers and SUCNR1 were analyzed in HT29 cells treated with succinate and/or an inflammatory cocktail and transfected with SUCNR1 siRNA in a murine DSS model, and in intestinal resections from 15 UC and non-IBD patients. Results showed that this receptor mediated the inflammasome, priming both in vitro in HT29 cells and in vivo in a murine chronic DSS-colitis model. Moreover, SUNCR1 was also found to be involved in the activation of the inflammatory pathways NF?B and ERK pathways, even in basal conditions, since the transient knock-down of this receptor significantly reduced the constitutive levels of pERK-1/2 and pNF?B and impaired LPS-induced inflammation. Finally, UC patients showed a significant increase in the expression of SUCNR1 and several inflammasome components which correlated positively and significantly. Therefore, our results demonstrated a role for SUCNR1 in basal and stimulated inflammatory pathways in intestinal epithelial cells and suggested a pivotal role for this receptor in inflammasome activation in UC.MDPI2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://incliva.portalinvestigacion.com/publicaciones/16656BiomedicinesISSN: 22279059reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVAinstname:INCLIVAInglésinfo:eu-repo/semantics/openAccessoai:incliva.fundanetsuite.com:p166562026-06-07T16:35:31Z
dc.title.none.fl_str_mv SUCNR1 Mediates the Priming Step of the Inflammasome in Intestinal Epithelial Cells: Relevance in Ulcerative Colitis.
title SUCNR1 Mediates the Priming Step of the Inflammasome in Intestinal Epithelial Cells: Relevance in Ulcerative Colitis.
spellingShingle SUCNR1 Mediates the Priming Step of the Inflammasome in Intestinal Epithelial Cells: Relevance in Ulcerative Colitis.
Bauset, C
SUCNR1
Ulcerative Colitis
epithelial cells
title_short SUCNR1 Mediates the Priming Step of the Inflammasome in Intestinal Epithelial Cells: Relevance in Ulcerative Colitis.
title_full SUCNR1 Mediates the Priming Step of the Inflammasome in Intestinal Epithelial Cells: Relevance in Ulcerative Colitis.
title_fullStr SUCNR1 Mediates the Priming Step of the Inflammasome in Intestinal Epithelial Cells: Relevance in Ulcerative Colitis.
title_full_unstemmed SUCNR1 Mediates the Priming Step of the Inflammasome in Intestinal Epithelial Cells: Relevance in Ulcerative Colitis.
title_sort SUCNR1 Mediates the Priming Step of the Inflammasome in Intestinal Epithelial Cells: Relevance in Ulcerative Colitis.
dc.creator.none.fl_str_mv Bauset, C
Lis-Lopez, L
Coll, S
Gisbert-Ferrandiz, L
Macias-Ceja, DC
Seco-Cervera, M
Navarro, F
Esplugues, JV
Calatayud, S
Ortiz-Masia, D
Barrachina, MD
Cosin-Roger, J
author Bauset, C
author_facet Bauset, C
Lis-Lopez, L
Coll, S
Gisbert-Ferrandiz, L
Macias-Ceja, DC
Seco-Cervera, M
Navarro, F
Esplugues, JV
Calatayud, S
Ortiz-Masia, D
Barrachina, MD
Cosin-Roger, J
author_role author
author2 Lis-Lopez, L
Coll, S
Gisbert-Ferrandiz, L
Macias-Ceja, DC
Seco-Cervera, M
Navarro, F
Esplugues, JV
Calatayud, S
Ortiz-Masia, D
Barrachina, MD
Cosin-Roger, J
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv SUCNR1
Ulcerative Colitis
epithelial cells
topic SUCNR1
Ulcerative Colitis
epithelial cells
description Intestinal epithelial cells (IECs) constitute a defensive physical barrier in mucosal tissues and their disruption is involved in the etiopathogenesis of several inflammatory pathologies, such as Ulcerative Colitis (UC). Recently, the succinate receptor SUCNR1 was associated with the activation of inflammatory pathways in several cell types, but little is known about its role in IECs. We aimed to analyze the role of SUCNR1 in the inflammasome priming and its relevance in UC. Inflammatory and inflammasome markers and SUCNR1 were analyzed in HT29 cells treated with succinate and/or an inflammatory cocktail and transfected with SUCNR1 siRNA in a murine DSS model, and in intestinal resections from 15 UC and non-IBD patients. Results showed that this receptor mediated the inflammasome, priming both in vitro in HT29 cells and in vivo in a murine chronic DSS-colitis model. Moreover, SUNCR1 was also found to be involved in the activation of the inflammatory pathways NF?B and ERK pathways, even in basal conditions, since the transient knock-down of this receptor significantly reduced the constitutive levels of pERK-1/2 and pNF?B and impaired LPS-induced inflammation. Finally, UC patients showed a significant increase in the expression of SUCNR1 and several inflammasome components which correlated positively and significantly. Therefore, our results demonstrated a role for SUCNR1 in basal and stimulated inflammatory pathways in intestinal epithelial cells and suggested a pivotal role for this receptor in inflammasome activation in UC.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://incliva.portalinvestigacion.com/publicaciones/16656
url https://incliva.portalinvestigacion.com/publicaciones/16656
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Biomedicines
ISSN: 22279059
reponame:r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
instname:INCLIVA
instname_str INCLIVA
reponame_str r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
collection r-INCLIVA. Repositorio Institucional de Producción Científica de INCLIVA
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