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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/11517
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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 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/11336/11517 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 |
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CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
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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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13.22299 |