Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo

Autores
Bosisio, Daniela; Vulcano, Marisa; Del Prete, Annalisa; Sironi, Marina; Salvi, Valentina; Salogni, Laura; Riboldi, Elena; Leoni, Flavio; Dinarello, Charles A.; Girolomoni, Giampiero; Sozzani, Silvano
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Histone deacetylase (HDAC) inhibitors are small molecules inducing cell-cycle arrest, differentiation, and apoptosis, currently undergoing clinical trials as anticancer drugs. In addition, emerging evidence suggests HDAC inhibitors may have anti-inflammatory and immunomodulatory properties as well, although the molecular mechanisms remain poorly defined. Given the central role of dendritic cells (DC) in the induction and maintenance of the inflammatory and immune response, we investigated the effects of HDAC inhibitors on the maturation and activation of human monocyte-derived DC in the presence of LPS and IFN-γ. Our results show that the production of TH1- and TH17-inducing cytokines, namely IL-12 and IL-23, was inhibited by trichostatin A (72% and 52%, respectively) and suberoylanilide hydroxamic acid (86% and 83%). Strikingly, HDAC inhibitors were effective if added simultaneously as well as after the proinflammatory challenge, and their effect was not associated to a reduction of expression or function of LPS/IFN-γ receptors. These findings were confirmed in two different murine models. In addition, HDAC inhibitors selectively blocked the production of T H1-attracting chemokines CXCL9, CXCL10, and CXCL11. The reduction of TH1- and TH17-inducing cytokines as well as T H1-attracting chemokines may represent relevant mechanisms through which HDAC inhibitors at nonproapoptotic doses exert their immunomodulatory properties.
Fil: Bosisio, Daniela. University of Brescia; Italia
Fil: Vulcano, Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Del Prete, Annalisa. Università degli Studi di Bari; Italia
Fil: Sironi, Marina. University of Brescia; Italia
Fil: Salvi, Valentina. University of Brescia; Italia
Fil: Salogni, Laura. University of Brescia; Italia
Fil: Riboldi, Elena. University of Brescia; Italia
Fil: Leoni, Flavio. Centro Ricerche Italfarmaco; Italia
Fil: Dinarello, Charles A.. University of Colorado; Estados Unidos
Fil: Girolomoni, Giampiero. Universita di Verona; Italia
Fil: Sozzani, Silvano. University of Brescia; Italia
Materia
AUTOIMMUNITY
CHEMOKINES
DENDRITIC CELLS
TH1/TH2 CELLS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/162970
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/162970
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivoBosisio, DanielaVulcano, MarisaDel Prete, AnnalisaSironi, MarinaSalvi, ValentinaSalogni, LauraRiboldi, ElenaLeoni, FlavioDinarello, Charles A.Girolomoni, GiampieroSozzani, SilvanoAUTOIMMUNITYCHEMOKINESDENDRITIC CELLSTH1/TH2 CELLShttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3Histone deacetylase (HDAC) inhibitors are small molecules inducing cell-cycle arrest, differentiation, and apoptosis, currently undergoing clinical trials as anticancer drugs. In addition, emerging evidence suggests HDAC inhibitors may have anti-inflammatory and immunomodulatory properties as well, although the molecular mechanisms remain poorly defined. Given the central role of dendritic cells (DC) in the induction and maintenance of the inflammatory and immune response, we investigated the effects of HDAC inhibitors on the maturation and activation of human monocyte-derived DC in the presence of LPS and IFN-γ. Our results show that the production of TH1- and TH17-inducing cytokines, namely IL-12 and IL-23, was inhibited by trichostatin A (72% and 52%, respectively) and suberoylanilide hydroxamic acid (86% and 83%). Strikingly, HDAC inhibitors were effective if added simultaneously as well as after the proinflammatory challenge, and their effect was not associated to a reduction of expression or function of LPS/IFN-γ receptors. These findings were confirmed in two different murine models. In addition, HDAC inhibitors selectively blocked the production of T H1-attracting chemokines CXCL9, CXCL10, and CXCL11. The reduction of TH1- and TH17-inducing cytokines as well as T H1-attracting chemokines may represent relevant mechanisms through which HDAC inhibitors at nonproapoptotic doses exert their immunomodulatory properties.Fil: Bosisio, Daniela. University of Brescia; ItaliaFil: Vulcano, Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Del Prete, Annalisa. Università degli Studi di Bari; ItaliaFil: Sironi, Marina. University of Brescia; ItaliaFil: Salvi, Valentina. University of Brescia; ItaliaFil: Salogni, Laura. University of Brescia; ItaliaFil: Riboldi, Elena. University of Brescia; ItaliaFil: Leoni, Flavio. Centro Ricerche Italfarmaco; ItaliaFil: Dinarello, Charles A.. University of Colorado; Estados UnidosFil: Girolomoni, Giampiero. Universita di Verona; ItaliaFil: Sozzani, Silvano. University of Brescia; ItaliaFederation of American Societies for Experimental Biology2008-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/162970Bosisio, Daniela; Vulcano, Marisa; Del Prete, Annalisa; Sironi, Marina; Salvi, Valentina; et al.; Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo; Federation of American Societies for Experimental Biology; Journal of Leukocyte Biology; 84; 6; 12-2008; 1540-15480741-5400CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://jlb.onlinelibrary.wiley.com/doi/full/10.1189/jlb.0708401info:eu-repo/semantics/altIdentifier/doi/10.1189/jlb.0708401info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:14:22Zoai:ri.conicet.gov.ar:11336/162970instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:14:22.426CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo
title Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo
spellingShingle Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo
Bosisio, Daniela
AUTOIMMUNITY
CHEMOKINES
DENDRITIC CELLS
TH1/TH2 CELLS
title_short Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo
title_full Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo
title_fullStr Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo
title_full_unstemmed Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo
title_sort Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo
dc.creator.none.fl_str_mv Bosisio, Daniela
Vulcano, Marisa
Del Prete, Annalisa
Sironi, Marina
Salvi, Valentina
Salogni, Laura
Riboldi, Elena
Leoni, Flavio
Dinarello, Charles A.
Girolomoni, Giampiero
Sozzani, Silvano
author Bosisio, Daniela
author_facet Bosisio, Daniela
Vulcano, Marisa
Del Prete, Annalisa
Sironi, Marina
Salvi, Valentina
Salogni, Laura
Riboldi, Elena
Leoni, Flavio
Dinarello, Charles A.
Girolomoni, Giampiero
Sozzani, Silvano
author_role author
author2 Vulcano, Marisa
Del Prete, Annalisa
Sironi, Marina
Salvi, Valentina
Salogni, Laura
Riboldi, Elena
Leoni, Flavio
Dinarello, Charles A.
Girolomoni, Giampiero
Sozzani, Silvano
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv AUTOIMMUNITY
CHEMOKINES
DENDRITIC CELLS
TH1/TH2 CELLS
topic AUTOIMMUNITY
CHEMOKINES
DENDRITIC CELLS
TH1/TH2 CELLS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Histone deacetylase (HDAC) inhibitors are small molecules inducing cell-cycle arrest, differentiation, and apoptosis, currently undergoing clinical trials as anticancer drugs. In addition, emerging evidence suggests HDAC inhibitors may have anti-inflammatory and immunomodulatory properties as well, although the molecular mechanisms remain poorly defined. Given the central role of dendritic cells (DC) in the induction and maintenance of the inflammatory and immune response, we investigated the effects of HDAC inhibitors on the maturation and activation of human monocyte-derived DC in the presence of LPS and IFN-γ. Our results show that the production of TH1- and TH17-inducing cytokines, namely IL-12 and IL-23, was inhibited by trichostatin A (72% and 52%, respectively) and suberoylanilide hydroxamic acid (86% and 83%). Strikingly, HDAC inhibitors were effective if added simultaneously as well as after the proinflammatory challenge, and their effect was not associated to a reduction of expression or function of LPS/IFN-γ receptors. These findings were confirmed in two different murine models. In addition, HDAC inhibitors selectively blocked the production of T H1-attracting chemokines CXCL9, CXCL10, and CXCL11. The reduction of TH1- and TH17-inducing cytokines as well as T H1-attracting chemokines may represent relevant mechanisms through which HDAC inhibitors at nonproapoptotic doses exert their immunomodulatory properties.
Fil: Bosisio, Daniela. University of Brescia; Italia
Fil: Vulcano, Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Del Prete, Annalisa. Università degli Studi di Bari; Italia
Fil: Sironi, Marina. University of Brescia; Italia
Fil: Salvi, Valentina. University of Brescia; Italia
Fil: Salogni, Laura. University of Brescia; Italia
Fil: Riboldi, Elena. University of Brescia; Italia
Fil: Leoni, Flavio. Centro Ricerche Italfarmaco; Italia
Fil: Dinarello, Charles A.. University of Colorado; Estados Unidos
Fil: Girolomoni, Giampiero. Universita di Verona; Italia
Fil: Sozzani, Silvano. University of Brescia; Italia
description Histone deacetylase (HDAC) inhibitors are small molecules inducing cell-cycle arrest, differentiation, and apoptosis, currently undergoing clinical trials as anticancer drugs. In addition, emerging evidence suggests HDAC inhibitors may have anti-inflammatory and immunomodulatory properties as well, although the molecular mechanisms remain poorly defined. Given the central role of dendritic cells (DC) in the induction and maintenance of the inflammatory and immune response, we investigated the effects of HDAC inhibitors on the maturation and activation of human monocyte-derived DC in the presence of LPS and IFN-γ. Our results show that the production of TH1- and TH17-inducing cytokines, namely IL-12 and IL-23, was inhibited by trichostatin A (72% and 52%, respectively) and suberoylanilide hydroxamic acid (86% and 83%). Strikingly, HDAC inhibitors were effective if added simultaneously as well as after the proinflammatory challenge, and their effect was not associated to a reduction of expression or function of LPS/IFN-γ receptors. These findings were confirmed in two different murine models. In addition, HDAC inhibitors selectively blocked the production of T H1-attracting chemokines CXCL9, CXCL10, and CXCL11. The reduction of TH1- and TH17-inducing cytokines as well as T H1-attracting chemokines may represent relevant mechanisms through which HDAC inhibitors at nonproapoptotic doses exert their immunomodulatory properties.
publishDate 2008
dc.date.none.fl_str_mv 2008-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/162970
Bosisio, Daniela; Vulcano, Marisa; Del Prete, Annalisa; Sironi, Marina; Salvi, Valentina; et al.; Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo; Federation of American Societies for Experimental Biology; Journal of Leukocyte Biology; 84; 6; 12-2008; 1540-1548
0741-5400
CONICET Digital
CONICET
url http://hdl.handle.net/11336/162970
identifier_str_mv Bosisio, Daniela; Vulcano, Marisa; Del Prete, Annalisa; Sironi, Marina; Salvi, Valentina; et al.; Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo; Federation of American Societies for Experimental Biology; Journal of Leukocyte Biology; 84; 6; 12-2008; 1540-1548
0741-5400
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://jlb.onlinelibrary.wiley.com/doi/full/10.1189/jlb.0708401
info:eu-repo/semantics/altIdentifier/doi/10.1189/jlb.0708401
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842980767391547392
score 12.993085

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