Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated Phenotype

Autores
Leimgruber, Carolina; Quintar, Amado Alfredo; García, Luciana Noemí; Petiti, Juan Pablo; de Paul, Ana Lucia; Maldonado, Cristina Alicia
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Prostate smooth muscle cells (pSMCs) are capable of responding to inflammatory stimuli by secreting proinflammatory products, which causes pSMCs to undergo dedifferentiation. Although it has been proposed that androgens decrease proinflammatory molecules in many cells and under various conditions, the role of testosterone in the prostate inflammatory microenvironment is still unclear. Therefore, our aim was to evaluate if testosterone was able to modulate the pSMCs response to bacterial LPS by stimulating primary pSMC cultures, containing testosterone or vehicle, with LPS (1 or 10mg/ml) for 24–48 h. The LPS challenge induced pSMCs dedifferentiation as evidenced by a decrease of calponin and alpha smooth muscle actin along with an increase of vimentin in a dose-dependent manner, whereas testosterone abrogated these alterations. Additionally, an ultrastructural analysis showed that pSMCs acquired a secretory profile after LPS and developed proteinopoietic organelles, while pSMCs preincubated with testosterone maintained a more differentiated phenotype. Testosterone downregulated the expression of surface TLR4 in control cells and inhibited any increase after LPS treatment. Moreover, testosterone prevented IkB-a degradation and the LPS-induced NF-kB nuclear translocation. Testosterone also decreased TNF-a and IL6 production by pSMCs after LPS as quantified by ELISA. Finally, we observed that testosterone inhibited the induction of pSMCs proliferation incited by LPS. Taken together, these results indicate that testosterone reduced the proinflammatory pSMCs response to LPS, with these cells being less reactive in the presence of androgens. In this context, testosterone might have a homeostatic role by contributing to preserve a contractile phenotype on pSMCs under inflammatory conditions.
Fil: Leimgruber, Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Quintar, Amado Alfredo. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: García, Luciana Noemí. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Petiti, Juan Pablo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: de Paul, Ana Lucia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Maldonado, Cristina Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Materia
Smooth Muscle Cells
Testosterone
Tlr4
Nfkb
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:11336/11517

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network_name_str CONICET Digital (CONICET)
spelling Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated PhenotypeLeimgruber, CarolinaQuintar, Amado AlfredoGarcía, Luciana NoemíPetiti, Juan Pablode Paul, Ana LuciaMaldonado, Cristina AliciaSmooth Muscle CellsTestosteroneTlr4Nfkbhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Prostate smooth muscle cells (pSMCs) are capable of responding to inflammatory stimuli by secreting proinflammatory products, which causes pSMCs to undergo dedifferentiation. Although it has been proposed that androgens decrease proinflammatory molecules in many cells and under various conditions, the role of testosterone in the prostate inflammatory microenvironment is still unclear. Therefore, our aim was to evaluate if testosterone was able to modulate the pSMCs response to bacterial LPS by stimulating primary pSMC cultures, containing testosterone or vehicle, with LPS (1 or 10mg/ml) for 24–48 h. The LPS challenge induced pSMCs dedifferentiation as evidenced by a decrease of calponin and alpha smooth muscle actin along with an increase of vimentin in a dose-dependent manner, whereas testosterone abrogated these alterations. Additionally, an ultrastructural analysis showed that pSMCs acquired a secretory profile after LPS and developed proteinopoietic organelles, while pSMCs preincubated with testosterone maintained a more differentiated phenotype. Testosterone downregulated the expression of surface TLR4 in control cells and inhibited any increase after LPS treatment. Moreover, testosterone prevented IkB-a degradation and the LPS-induced NF-kB nuclear translocation. Testosterone also decreased TNF-a and IL6 production by pSMCs after LPS as quantified by ELISA. Finally, we observed that testosterone inhibited the induction of pSMCs proliferation incited by LPS. Taken together, these results indicate that testosterone reduced the proinflammatory pSMCs response to LPS, with these cells being less reactive in the presence of androgens. In this context, testosterone might have a homeostatic role by contributing to preserve a contractile phenotype on pSMCs under inflammatory conditions.Fil: Leimgruber, Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; ArgentinaFil: Quintar, Amado Alfredo. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: García, Luciana Noemí. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; ArgentinaFil: Petiti, Juan Pablo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; ArgentinaFil: de Paul, Ana Lucia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; ArgentinaFil: Maldonado, Cristina Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; ArgentinaWiley2013-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/11517Leimgruber, Carolina; Quintar, Amado Alfredo; García, Luciana Noemí; Petiti, Juan Pablo; de Paul, Ana Lucia; et al.; Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated Phenotype; Wiley; Journal Of Cellular Physiology; 228; 7; 7-2013; 1551–15600021-95411097-4652enginfo:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.24314info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jcp.24314/abstractinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:45:04Zoai:ri.conicet.gov.ar:11336/11517instacron: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:34982025-10-15 14:45:04.75CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated Phenotype
title Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated Phenotype
spellingShingle Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated Phenotype
Leimgruber, Carolina
Smooth Muscle Cells
Testosterone
Tlr4
Nfkb
title_short Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated Phenotype
title_full Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated Phenotype
title_fullStr Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated Phenotype
title_full_unstemmed Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated Phenotype
title_sort Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated Phenotype
dc.creator.none.fl_str_mv Leimgruber, Carolina
Quintar, Amado Alfredo
García, Luciana Noemí
Petiti, Juan Pablo
de Paul, Ana Lucia
Maldonado, Cristina Alicia
author Leimgruber, Carolina
author_facet Leimgruber, Carolina
Quintar, Amado Alfredo
García, Luciana Noemí
Petiti, Juan Pablo
de Paul, Ana Lucia
Maldonado, Cristina Alicia
author_role author
author2 Quintar, Amado Alfredo
García, Luciana Noemí
Petiti, Juan Pablo
de Paul, Ana Lucia
Maldonado, Cristina Alicia
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Smooth Muscle Cells
Testosterone
Tlr4
Nfkb
topic Smooth Muscle Cells
Testosterone
Tlr4
Nfkb
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Prostate smooth muscle cells (pSMCs) are capable of responding to inflammatory stimuli by secreting proinflammatory products, which causes pSMCs to undergo dedifferentiation. Although it has been proposed that androgens decrease proinflammatory molecules in many cells and under various conditions, the role of testosterone in the prostate inflammatory microenvironment is still unclear. Therefore, our aim was to evaluate if testosterone was able to modulate the pSMCs response to bacterial LPS by stimulating primary pSMC cultures, containing testosterone or vehicle, with LPS (1 or 10mg/ml) for 24–48 h. The LPS challenge induced pSMCs dedifferentiation as evidenced by a decrease of calponin and alpha smooth muscle actin along with an increase of vimentin in a dose-dependent manner, whereas testosterone abrogated these alterations. Additionally, an ultrastructural analysis showed that pSMCs acquired a secretory profile after LPS and developed proteinopoietic organelles, while pSMCs preincubated with testosterone maintained a more differentiated phenotype. Testosterone downregulated the expression of surface TLR4 in control cells and inhibited any increase after LPS treatment. Moreover, testosterone prevented IkB-a degradation and the LPS-induced NF-kB nuclear translocation. Testosterone also decreased TNF-a and IL6 production by pSMCs after LPS as quantified by ELISA. Finally, we observed that testosterone inhibited the induction of pSMCs proliferation incited by LPS. Taken together, these results indicate that testosterone reduced the proinflammatory pSMCs response to LPS, with these cells being less reactive in the presence of androgens. In this context, testosterone might have a homeostatic role by contributing to preserve a contractile phenotype on pSMCs under inflammatory conditions.
Fil: Leimgruber, Carolina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones En Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Quintar, Amado Alfredo. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina
Fil: García, Luciana Noemí. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Petiti, Juan Pablo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: de Paul, Ana Lucia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
Fil: Maldonado, Cristina Alicia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Cordoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Microscopia Electronica; Argentina
description Prostate smooth muscle cells (pSMCs) are capable of responding to inflammatory stimuli by secreting proinflammatory products, which causes pSMCs to undergo dedifferentiation. Although it has been proposed that androgens decrease proinflammatory molecules in many cells and under various conditions, the role of testosterone in the prostate inflammatory microenvironment is still unclear. Therefore, our aim was to evaluate if testosterone was able to modulate the pSMCs response to bacterial LPS by stimulating primary pSMC cultures, containing testosterone or vehicle, with LPS (1 or 10mg/ml) for 24–48 h. The LPS challenge induced pSMCs dedifferentiation as evidenced by a decrease of calponin and alpha smooth muscle actin along with an increase of vimentin in a dose-dependent manner, whereas testosterone abrogated these alterations. Additionally, an ultrastructural analysis showed that pSMCs acquired a secretory profile after LPS and developed proteinopoietic organelles, while pSMCs preincubated with testosterone maintained a more differentiated phenotype. Testosterone downregulated the expression of surface TLR4 in control cells and inhibited any increase after LPS treatment. Moreover, testosterone prevented IkB-a degradation and the LPS-induced NF-kB nuclear translocation. Testosterone also decreased TNF-a and IL6 production by pSMCs after LPS as quantified by ELISA. Finally, we observed that testosterone inhibited the induction of pSMCs proliferation incited by LPS. Taken together, these results indicate that testosterone reduced the proinflammatory pSMCs response to LPS, with these cells being less reactive in the presence of androgens. In this context, testosterone might have a homeostatic role by contributing to preserve a contractile phenotype on pSMCs under inflammatory conditions.
publishDate 2013
dc.date.none.fl_str_mv 2013-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/11517
Leimgruber, Carolina; Quintar, Amado Alfredo; García, Luciana Noemí; Petiti, Juan Pablo; de Paul, Ana Lucia; et al.; Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated Phenotype; Wiley; Journal Of Cellular Physiology; 228; 7; 7-2013; 1551–1560
0021-9541
1097-4652
url http://hdl.handle.net/11336/11517
identifier_str_mv Leimgruber, Carolina; Quintar, Amado Alfredo; García, Luciana Noemí; Petiti, Juan Pablo; de Paul, Ana Lucia; et al.; Testosterone abrogates TLR4 activation in prostate smooth muscle cells contributing to the preservation of a differentiated Phenotype; Wiley; Journal Of Cellular Physiology; 228; 7; 7-2013; 1551–1560
0021-9541
1097-4652
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.24314
info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/jcp.24314/abstract
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 Wiley
publisher.none.fl_str_mv Wiley
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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