GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A

Autores
Barcala Tabarrozzi, Andrés Ezequiel; Andreone, Luz; Deckers, Julie; Castro, Carla Noemí; Gimeno, Maria Laura; Ariolfo, Laura; Berguer, Paula Mercedes; Antunica Noguerol, María de Las Nieves; Liberman, Ana Clara; Vettorazzi, Sabine; Tuckermann, Jan P.; De Bosscher, Karolien; Perone, Marcelo Javier
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Dendritic cells (DC) initiate the adaptive immune response. Glucocorticoids (GCs) down-modulate the function of DC. Compound A (CpdA, (2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride) is a plant-derived GR-ligand with marked dissociative properties. We investigated the effects of CpdA on in vitro generated GM-CSF-conditioned bone marrow-derived DC (BMDC). CpdA-exposed BMDC exhibited low expression of cell-surface molecules and diminution of the release of proinflammatory cytokines upon LPS stimulation; processes associated with BMDC maturation and activation. CpdA-treated BMDC were inefficient at Ag capture via mannose receptor-mediated endocytosis and displayed reduced T-cell priming. CpdA prevented the LPS-induced rise in pErk1/2 and pP38, kinases involved in TLR4 signaling. CpdA fully inhibited LPS-induced pAktSer473, a marker associated with the generation of tolerogenic DC. We used pharmacological blockade and selective genetic loss-of-function tools and demonstrated GR-independent inhibitory effects of CpdA in BMDC. Mechanistically, CpdA-mediated inactivation of the NF-κB intracellular signaling pathway was associated with a short-circuiting of pErk1/2 and pP38 upstream signaling. Assessment of the in vivo function of CpdA-treated BMDC pulsed with the hapten trinitrobenzenesulfonic acid showed impaired cell-mediated contact hypersensitivity. Collectively, we provide evidence that CpdA is an effective BMDC modulator that might have a benefit for immune disorders, even when GR is not directly targeted.
Fil: Barcala Tabarrozzi, Andrés Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Andreone, Luz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Deckers, Julie. University of Ghent; Bélgica
Fil: Castro, Carla Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Gimeno, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Ariolfo, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Berguer, Paula Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Antunica Noguerol, María de Las Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Liberman, Ana Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Vettorazzi, Sabine. Universitat Ulm; Alemania
Fil: Tuckermann, Jan P.. Universitat Ulm; Alemania
Fil: De Bosscher, Karolien. University of Ghent; Bélgica
Fil: Perone, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Materia
GLUCOCORTICOID RECEPTOR
COMPOUND A
TLR4
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:11336/20866
Acceder
id CONICETDig_3b508175f0a4d99afa153681840b2402
oai_identifier_str oai:ri.conicet.gov.ar:11336/20866
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound ABarcala Tabarrozzi, Andrés EzequielAndreone, LuzDeckers, JulieCastro, Carla NoemíGimeno, Maria LauraAriolfo, LauraBerguer, Paula MercedesAntunica Noguerol, María de Las NievesLiberman, Ana ClaraVettorazzi, SabineTuckermann, Jan P.De Bosscher, KarolienPerone, Marcelo JavierGLUCOCORTICOID RECEPTORCOMPOUND ATLR4https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Dendritic cells (DC) initiate the adaptive immune response. Glucocorticoids (GCs) down-modulate the function of DC. Compound A (CpdA, (2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride) is a plant-derived GR-ligand with marked dissociative properties. We investigated the effects of CpdA on in vitro generated GM-CSF-conditioned bone marrow-derived DC (BMDC). CpdA-exposed BMDC exhibited low expression of cell-surface molecules and diminution of the release of proinflammatory cytokines upon LPS stimulation; processes associated with BMDC maturation and activation. CpdA-treated BMDC were inefficient at Ag capture via mannose receptor-mediated endocytosis and displayed reduced T-cell priming. CpdA prevented the LPS-induced rise in pErk1/2 and pP38, kinases involved in TLR4 signaling. CpdA fully inhibited LPS-induced pAktSer473, a marker associated with the generation of tolerogenic DC. We used pharmacological blockade and selective genetic loss-of-function tools and demonstrated GR-independent inhibitory effects of CpdA in BMDC. Mechanistically, CpdA-mediated inactivation of the NF-κB intracellular signaling pathway was associated with a short-circuiting of pErk1/2 and pP38 upstream signaling. Assessment of the in vivo function of CpdA-treated BMDC pulsed with the hapten trinitrobenzenesulfonic acid showed impaired cell-mediated contact hypersensitivity. Collectively, we provide evidence that CpdA is an effective BMDC modulator that might have a benefit for immune disorders, even when GR is not directly targeted.Fil: Barcala Tabarrozzi, Andrés Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Andreone, Luz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Deckers, Julie. University of Ghent; BélgicaFil: Castro, Carla Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Gimeno, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Ariolfo, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Berguer, Paula Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Antunica Noguerol, María de Las Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Liberman, Ana Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Vettorazzi, Sabine. Universitat Ulm; AlemaniaFil: Tuckermann, Jan P.. Universitat Ulm; AlemaniaFil: De Bosscher, Karolien. University of Ghent; BélgicaFil: Perone, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaSpringer Nature2016-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/20866Barcala Tabarrozzi, Andrés Ezequiel; Andreone, Luz; Deckers, Julie; Castro, Carla Noemí; Gimeno, Maria Laura; et al.; GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A; Springer Nature; Scientific Reports; 6; 11-2016; 1-162045-23222045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/srep36646info:eu-repo/semantics/altIdentifier/doi/10.1038/srep36646info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:47:42Zoai:ri.conicet.gov.ar:11336/20866instacron: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:34982025-09-29 09:47:43.147CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A
title GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A
spellingShingle GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A
Barcala Tabarrozzi, Andrés Ezequiel
GLUCOCORTICOID RECEPTOR
COMPOUND A
TLR4
title_short GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A
title_full GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A
title_fullStr GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A
title_full_unstemmed GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A
title_sort GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A
dc.creator.none.fl_str_mv Barcala Tabarrozzi, Andrés Ezequiel
Andreone, Luz
Deckers, Julie
Castro, Carla Noemí
Gimeno, Maria Laura
Ariolfo, Laura
Berguer, Paula Mercedes
Antunica Noguerol, María de Las Nieves
Liberman, Ana Clara
Vettorazzi, Sabine
Tuckermann, Jan P.
De Bosscher, Karolien
Perone, Marcelo Javier
author Barcala Tabarrozzi, Andrés Ezequiel
author_facet Barcala Tabarrozzi, Andrés Ezequiel
Andreone, Luz
Deckers, Julie
Castro, Carla Noemí
Gimeno, Maria Laura
Ariolfo, Laura
Berguer, Paula Mercedes
Antunica Noguerol, María de Las Nieves
Liberman, Ana Clara
Vettorazzi, Sabine
Tuckermann, Jan P.
De Bosscher, Karolien
Perone, Marcelo Javier
author_role author
author2 Andreone, Luz
Deckers, Julie
Castro, Carla Noemí
Gimeno, Maria Laura
Ariolfo, Laura
Berguer, Paula Mercedes
Antunica Noguerol, María de Las Nieves
Liberman, Ana Clara
Vettorazzi, Sabine
Tuckermann, Jan P.
De Bosscher, Karolien
Perone, Marcelo Javier
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GLUCOCORTICOID RECEPTOR
COMPOUND A
TLR4
topic GLUCOCORTICOID RECEPTOR
COMPOUND A
TLR4
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Dendritic cells (DC) initiate the adaptive immune response. Glucocorticoids (GCs) down-modulate the function of DC. Compound A (CpdA, (2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride) is a plant-derived GR-ligand with marked dissociative properties. We investigated the effects of CpdA on in vitro generated GM-CSF-conditioned bone marrow-derived DC (BMDC). CpdA-exposed BMDC exhibited low expression of cell-surface molecules and diminution of the release of proinflammatory cytokines upon LPS stimulation; processes associated with BMDC maturation and activation. CpdA-treated BMDC were inefficient at Ag capture via mannose receptor-mediated endocytosis and displayed reduced T-cell priming. CpdA prevented the LPS-induced rise in pErk1/2 and pP38, kinases involved in TLR4 signaling. CpdA fully inhibited LPS-induced pAktSer473, a marker associated with the generation of tolerogenic DC. We used pharmacological blockade and selective genetic loss-of-function tools and demonstrated GR-independent inhibitory effects of CpdA in BMDC. Mechanistically, CpdA-mediated inactivation of the NF-κB intracellular signaling pathway was associated with a short-circuiting of pErk1/2 and pP38 upstream signaling. Assessment of the in vivo function of CpdA-treated BMDC pulsed with the hapten trinitrobenzenesulfonic acid showed impaired cell-mediated contact hypersensitivity. Collectively, we provide evidence that CpdA is an effective BMDC modulator that might have a benefit for immune disorders, even when GR is not directly targeted.
Fil: Barcala Tabarrozzi, Andrés Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Andreone, Luz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Deckers, Julie. University of Ghent; Bélgica
Fil: Castro, Carla Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Gimeno, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Ariolfo, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Berguer, Paula Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Antunica Noguerol, María de Las Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Liberman, Ana Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Vettorazzi, Sabine. Universitat Ulm; Alemania
Fil: Tuckermann, Jan P.. Universitat Ulm; Alemania
Fil: De Bosscher, Karolien. University of Ghent; Bélgica
Fil: Perone, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Pque. Centenario. Instituto de Investigación En Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
description Dendritic cells (DC) initiate the adaptive immune response. Glucocorticoids (GCs) down-modulate the function of DC. Compound A (CpdA, (2-(4-acetoxyphenyl)-2-chloro-N-methyl-ethylammonium chloride) is a plant-derived GR-ligand with marked dissociative properties. We investigated the effects of CpdA on in vitro generated GM-CSF-conditioned bone marrow-derived DC (BMDC). CpdA-exposed BMDC exhibited low expression of cell-surface molecules and diminution of the release of proinflammatory cytokines upon LPS stimulation; processes associated with BMDC maturation and activation. CpdA-treated BMDC were inefficient at Ag capture via mannose receptor-mediated endocytosis and displayed reduced T-cell priming. CpdA prevented the LPS-induced rise in pErk1/2 and pP38, kinases involved in TLR4 signaling. CpdA fully inhibited LPS-induced pAktSer473, a marker associated with the generation of tolerogenic DC. We used pharmacological blockade and selective genetic loss-of-function tools and demonstrated GR-independent inhibitory effects of CpdA in BMDC. Mechanistically, CpdA-mediated inactivation of the NF-κB intracellular signaling pathway was associated with a short-circuiting of pErk1/2 and pP38 upstream signaling. Assessment of the in vivo function of CpdA-treated BMDC pulsed with the hapten trinitrobenzenesulfonic acid showed impaired cell-mediated contact hypersensitivity. Collectively, we provide evidence that CpdA is an effective BMDC modulator that might have a benefit for immune disorders, even when GR is not directly targeted.
publishDate 2016
dc.date.none.fl_str_mv 2016-11
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/11336/20866
Barcala Tabarrozzi, Andrés Ezequiel; Andreone, Luz; Deckers, Julie; Castro, Carla Noemí; Gimeno, Maria Laura; et al.; GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A; Springer Nature; Scientific Reports; 6; 11-2016; 1-16
2045-2322
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/20866
identifier_str_mv Barcala Tabarrozzi, Andrés Ezequiel; Andreone, Luz; Deckers, Julie; Castro, Carla Noemí; Gimeno, Maria Laura; et al.; GR-independent down-modulation on GM-CSF bone marrow-derived dendritic cells by the selective glucocorticoid receptor modulator Compound A; Springer Nature; Scientific Reports; 6; 11-2016; 1-16
2045-2322
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://www.nature.com/articles/srep36646
info:eu-repo/semantics/altIdentifier/doi/10.1038/srep36646
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 Springer Nature
publisher.none.fl_str_mv Springer Nature
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
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score 13.070432

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