Sirtuin 1 is a key regulator of the interleukin-12 p70/interleukin-23 balance in human dendritic cells

Stimulation of human dendritic cells with the fungal surrogate zymosan produces IL-23 and a low amount of IL-12 p70. Trans-repression of il12a transcription, which encodes IL-12 p35 chain, by proteins of the Notch family and lysine deacetylation reactions have been reported as the underlying mechani...

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Authors: Álvarez, Yolanda, Rodríguez Peña, Mario, Municio, Cristina, Hugo, Etzel, Alonso, Sara, Ibarrola, Nieves, Fernández, Nieves, Sánchez Crespo, Mariano
Format: article
Status:Published version
Publication Date:2012
Country:España
Institution:Consejo Superior de Investigaciones Científicas (CSIC)
Repository:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/116657
Online Access:http://hdl.handle.net/10261/116657
Access Level:Open access
Keyword:NF-κB (NF-KB)
Sirtuins
NAD
Histone deacetylases
Dendritic cells
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spelling Sirtuin 1 is a key regulator of the interleukin-12 p70/interleukin-23 balance in human dendritic cellsÁlvarez, YolandaRodríguez Peña, MarioMunicio, CristinaHugo, EtzelAlonso, SaraIbarrola, NievesFernández, NievesSánchez Crespo, MarianoNF-κB (NF-KB)SirtuinsNADHistone deacetylasesDendritic cellsStimulation of human dendritic cells with the fungal surrogate zymosan produces IL-23 and a low amount of IL-12 p70. Trans-repression of il12a transcription, which encodes IL-12 p35 chain, by proteins of the Notch family and lysine deacetylation reactions have been reported as the underlying mechanisms, but a number of questions remain to be addressed. Zymosan produced the location of sirtuin 1 (SIRT1) to the nucleus, enhanced its association with the il12a promoter, increased the nuclear concentration of the SIRT1 co-substrate NAD +, and decreased chromatin accessibility in the nucleosome-1 of il12a, which contains a κB-site. The involvement of deacetylation reactions in the inhibition of il12a transcription was supported by the absence of Ac-Lys-14-histone H3 in dendritic cells treated with zymosan upon coimmunoprecipitation of transducin- like enhancer of split. In contrast, we did not obtain evidence of a possible effect of SIRT1 through the deacetylation of c-Rel, the central element of the NF-κB family involved in il12a regulation. These data indicate that an enhancement of SIRT1 activity in response to phagocytic stimuli may reduce the accessibility of c-Rel to the il12a promoter and its transcriptional activation, thus regulating the IL-12 p70/IL-23 balance and modulating the ongoing immune response. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.This work was supported by Plan Nacional de Salud y Farmacia Grants SAF2007-60446 and SAF2010-15070, Fundación Ramón Areces, Red Temática de Investigación Cardiovascular, and Junta de Castilla y León Grant CSI003A11-2.Peer ReviewedAmerican Society for Biochemistry and Molecular BiologyMinisterio de Sanidad, Servicios Sociales e Igualdad (España)Fundación Ramón ArecesInstituto de Salud Carlos IIIJunta de Castilla y LeónConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2015201520122015info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/116657reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1166572026-05-22T06:33:51Z
dc.title.none.fl_str_mv Sirtuin 1 is a key regulator of the interleukin-12 p70/interleukin-23 balance in human dendritic cells
title Sirtuin 1 is a key regulator of the interleukin-12 p70/interleukin-23 balance in human dendritic cells
spellingShingle Sirtuin 1 is a key regulator of the interleukin-12 p70/interleukin-23 balance in human dendritic cells
Álvarez, Yolanda
NF-κB (NF-KB)
Sirtuins
NAD
Histone deacetylases
Dendritic cells
title_short Sirtuin 1 is a key regulator of the interleukin-12 p70/interleukin-23 balance in human dendritic cells
title_full Sirtuin 1 is a key regulator of the interleukin-12 p70/interleukin-23 balance in human dendritic cells
title_fullStr Sirtuin 1 is a key regulator of the interleukin-12 p70/interleukin-23 balance in human dendritic cells
title_full_unstemmed Sirtuin 1 is a key regulator of the interleukin-12 p70/interleukin-23 balance in human dendritic cells
title_sort Sirtuin 1 is a key regulator of the interleukin-12 p70/interleukin-23 balance in human dendritic cells
dc.creator.none.fl_str_mv Álvarez, Yolanda
Rodríguez Peña, Mario
Municio, Cristina
Hugo, Etzel
Alonso, Sara
Ibarrola, Nieves
Fernández, Nieves
Sánchez Crespo, Mariano
author Álvarez, Yolanda
author_facet Álvarez, Yolanda
Rodríguez Peña, Mario
Municio, Cristina
Hugo, Etzel
Alonso, Sara
Ibarrola, Nieves
Fernández, Nieves
Sánchez Crespo, Mariano
author_role author
author2 Rodríguez Peña, Mario
Municio, Cristina
Hugo, Etzel
Alonso, Sara
Ibarrola, Nieves
Fernández, Nieves
Sánchez Crespo, Mariano
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Sanidad, Servicios Sociales e Igualdad (España)
Fundación Ramón Areces
Instituto de Salud Carlos III
Junta de Castilla y León
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv NF-κB (NF-KB)
Sirtuins
NAD
Histone deacetylases
Dendritic cells
topic NF-κB (NF-KB)
Sirtuins
NAD
Histone deacetylases
Dendritic cells
description Stimulation of human dendritic cells with the fungal surrogate zymosan produces IL-23 and a low amount of IL-12 p70. Trans-repression of il12a transcription, which encodes IL-12 p35 chain, by proteins of the Notch family and lysine deacetylation reactions have been reported as the underlying mechanisms, but a number of questions remain to be addressed. Zymosan produced the location of sirtuin 1 (SIRT1) to the nucleus, enhanced its association with the il12a promoter, increased the nuclear concentration of the SIRT1 co-substrate NAD +, and decreased chromatin accessibility in the nucleosome-1 of il12a, which contains a κB-site. The involvement of deacetylation reactions in the inhibition of il12a transcription was supported by the absence of Ac-Lys-14-histone H3 in dendritic cells treated with zymosan upon coimmunoprecipitation of transducin- like enhancer of split. In contrast, we did not obtain evidence of a possible effect of SIRT1 through the deacetylation of c-Rel, the central element of the NF-κB family involved in il12a regulation. These data indicate that an enhancement of SIRT1 activity in response to phagocytic stimuli may reduce the accessibility of c-Rel to the il12a promoter and its transcriptional activation, thus regulating the IL-12 p70/IL-23 balance and modulating the ongoing immune response. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
publishDate 2012
dc.date.none.fl_str_mv 2012
2015
2015
2015
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/10261/116657
url http://hdl.handle.net/10261/116657
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
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 15,812429

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