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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 principales: Bauset, Cristina, Lis-Lopez, Lluis, Coll, Sandra, Gisbert-Ferrándiz, Laura, Macias-Ceja, Dulce C., Seco-Cervera, Marta, Navarro, Francisco, Esplugues, Juan V., Calatayud, Sara, Ortiz-Masia, Dolores, Barrachina, Maria D., Cosín-Roger, Jesús
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945150/
https://www.ncbi.nlm.nih.gov/pubmed/35327334
http://dx.doi.org/10.3390/biomedicines10030532
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author Bauset, Cristina
Lis-Lopez, Lluis
Coll, Sandra
Gisbert-Ferrándiz, Laura
Macias-Ceja, Dulce C.
Seco-Cervera, Marta
Navarro, Francisco
Esplugues, Juan V.
Calatayud, Sara
Ortiz-Masia, Dolores
Barrachina, Maria D.
Cosín-Roger, Jesús
author_facet Bauset, Cristina
Lis-Lopez, Lluis
Coll, Sandra
Gisbert-Ferrándiz, Laura
Macias-Ceja, Dulce C.
Seco-Cervera, Marta
Navarro, Francisco
Esplugues, Juan V.
Calatayud, Sara
Ortiz-Masia, Dolores
Barrachina, Maria D.
Cosín-Roger, Jesús
author_sort Bauset, Cristina
collection PubMed
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 NFкB 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 pNFкB 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.
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spelling pubmed-89451502022-03-25 SUCNR1 Mediates the Priming Step of the Inflammasome in Intestinal Epithelial Cells: Relevance in Ulcerative Colitis Bauset, Cristina Lis-Lopez, Lluis Coll, Sandra Gisbert-Ferrándiz, Laura Macias-Ceja, Dulce C. Seco-Cervera, Marta Navarro, Francisco Esplugues, Juan V. Calatayud, Sara Ortiz-Masia, Dolores Barrachina, Maria D. Cosín-Roger, Jesús Biomedicines Article 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 NFкB 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 pNFкB 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. MDPI 2022-02-24 /pmc/articles/PMC8945150/ /pubmed/35327334 http://dx.doi.org/10.3390/biomedicines10030532 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bauset, Cristina
Lis-Lopez, Lluis
Coll, Sandra
Gisbert-Ferrándiz, Laura
Macias-Ceja, Dulce C.
Seco-Cervera, Marta
Navarro, Francisco
Esplugues, Juan V.
Calatayud, Sara
Ortiz-Masia, Dolores
Barrachina, Maria D.
Cosín-Roger, Jesús
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
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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945150/
https://www.ncbi.nlm.nih.gov/pubmed/35327334
http://dx.doi.org/10.3390/biomedicines10030532
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