Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1
- Autores
- Villar, Silvina Raquel; Ronco, Maria Teresa; Fernandez Bussy, Rodrigo; Roggero, Edgardo Luis; Lepletier, Ailin; Manarin, Romina; Savino, Wilson; Perez, Ana Rosa; Bottasso, Oscar Adelmo
- Año de publicación
- 2013
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Adrenal steroidogenesis is under a complex regulation involving extrinsic and intrinsic adrenal factors. TNF-a is an inflammatory cytokine produced in response to tissue injury and several other stimuli. We have previously demonstrated that TNF-R1 knockout (TNF-R12/2) mice have a dysregulated synthesis of glucocorticoids (GCs) during Trypanosoma cruzi acute infection. Since TNF-a may influence GCs production, not only through the hypothalamus-pituitary axis, but also at the adrenal level, we now investigated the role of this cytokine on the adrenal GCs production. Wild type (WT) and TNF-R12/2 mice undergoing acute infection (Tc-WT and Tc-TNF-R12/2 groups), displayed adrenal hyperplasia together with increased GCs levels. Notably, systemic ACTH remained unchanged in Tc-WT and Tc-TNF-R12/2 compared with uninfected mice, suggesting some degree of ACTH-independence of GCs synthesis. TNF-a expression was increased within the adrenal gland from both infected mouse groups, with Tc-WT mice showing an augmented TNF-R1 expression. Tc-WT mice showed increased levels of P-p38 and P-ERK compared to uninfected WT animals, whereas Tc-TNF-R12/2 mice had increased p38 and JNK phosphorylation respect to Tc-WT mice. Strikingly, adrenal NF-kB and AP-1 activation during infection was blunted in Tc-TNF-R12/2 mice. The accumulation of mRNAs for steroidogenic acute regulatory protein and cytochrome P450 were significantly increased in both Tc-WT and Tc-TNF-R12/2 mice; being much more augmented in the latter group, which also had remarkably increased GCs levels. TNF-a emerges as a potent modulator of steroidogenesis in adrenocortical cells during T. cruzi infection in which MAPK pathways, NF-kB and AP-1 seem to play a role in the adrenal synthesis of pro-inflammatory cytokines and enzymes regulating GCs synthesis. These results suggest the existence of an intrinsic immune-adrenal interaction involved in the dysregulated synthesis of GCs during murine Chagas disease.
Fil: Villar, Silvina Raquel. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia;
Fil: Ronco, Maria Teresa. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas;
Fil: Fernandez Bussy, Rodrigo. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia;
Fil: Roggero, Edgardo Luis. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia;
Fil: Lepletier, Ailin. Ministerio de Salud de Brasil. Fundacion Oswaldo Cruz;
Fil: Romina Manarin. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia;
Fil: Savino, Wilson. Ministerio de Salud de Brasil. Fundacion Oswaldo Cruz;
Fil: Perez, Ana Rosa. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia;
Fil: Bottasso, Oscar Adelmo. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia; - Materia
-
Glucocorticoides
Factor de Necrosis tumoral
Adrenales
Trypanosoma cruzi - 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:11336/511
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oai:ri.conicet.gov.ar:11336/511 |
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Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1Villar, Silvina RaquelRonco, Maria TeresaFernandez Bussy, RodrigoRoggero, Edgardo LuisLepletier, AilinManarin, RominaSavino, WilsonPerez, Ana RosaBottasso, Oscar AdelmoGlucocorticoidesFactor de Necrosis tumoralAdrenalesTrypanosoma cruzihttps://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.1Adrenal steroidogenesis is under a complex regulation involving extrinsic and intrinsic adrenal factors. TNF-a is an inflammatory cytokine produced in response to tissue injury and several other stimuli. We have previously demonstrated that TNF-R1 knockout (TNF-R12/2) mice have a dysregulated synthesis of glucocorticoids (GCs) during Trypanosoma cruzi acute infection. Since TNF-a may influence GCs production, not only through the hypothalamus-pituitary axis, but also at the adrenal level, we now investigated the role of this cytokine on the adrenal GCs production. Wild type (WT) and TNF-R12/2 mice undergoing acute infection (Tc-WT and Tc-TNF-R12/2 groups), displayed adrenal hyperplasia together with increased GCs levels. Notably, systemic ACTH remained unchanged in Tc-WT and Tc-TNF-R12/2 compared with uninfected mice, suggesting some degree of ACTH-independence of GCs synthesis. TNF-a expression was increased within the adrenal gland from both infected mouse groups, with Tc-WT mice showing an augmented TNF-R1 expression. Tc-WT mice showed increased levels of P-p38 and P-ERK compared to uninfected WT animals, whereas Tc-TNF-R12/2 mice had increased p38 and JNK phosphorylation respect to Tc-WT mice. Strikingly, adrenal NF-kB and AP-1 activation during infection was blunted in Tc-TNF-R12/2 mice. The accumulation of mRNAs for steroidogenic acute regulatory protein and cytochrome P450 were significantly increased in both Tc-WT and Tc-TNF-R12/2 mice; being much more augmented in the latter group, which also had remarkably increased GCs levels. TNF-a emerges as a potent modulator of steroidogenesis in adrenocortical cells during T. cruzi infection in which MAPK pathways, NF-kB and AP-1 seem to play a role in the adrenal synthesis of pro-inflammatory cytokines and enzymes regulating GCs synthesis. These results suggest the existence of an intrinsic immune-adrenal interaction involved in the dysregulated synthesis of GCs during murine Chagas disease.Fil: Villar, Silvina Raquel. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia;Fil: Ronco, Maria Teresa. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas;Fil: Fernandez Bussy, Rodrigo. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia;Fil: Roggero, Edgardo Luis. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia;Fil: Lepletier, Ailin. Ministerio de Salud de Brasil. Fundacion Oswaldo Cruz;Fil: Romina Manarin. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia;Fil: Savino, Wilson. Ministerio de Salud de Brasil. Fundacion Oswaldo Cruz;Fil: Perez, Ana Rosa. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia;Fil: Bottasso, Oscar Adelmo. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia;Public Library Science2013-05-22info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/511Villar, Silvina Raquel; Ronco, Maria Teresa; Fernandez Bussy, Rodrigo; Roggero, Edgardo Luis; Lepletier, Ailin; Romina Manarin; Savino, Wilson ; Perez, Ana Rosa; Bottasso, Oscar Adelmo; Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1; Public Library Science; Plos One; 8; 5; 22-5-2013; 1-13;1932-6203enginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0063814info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:52:12Zoai:ri.conicet.gov.ar:11336/511instacron: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 09:52:12.913CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1 |
title |
Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1 |
spellingShingle |
Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1 Villar, Silvina Raquel Glucocorticoides Factor de Necrosis tumoral Adrenales Trypanosoma cruzi |
title_short |
Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1 |
title_full |
Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1 |
title_fullStr |
Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1 |
title_full_unstemmed |
Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1 |
title_sort |
Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1 |
dc.creator.none.fl_str_mv |
Villar, Silvina Raquel Ronco, Maria Teresa Fernandez Bussy, Rodrigo Roggero, Edgardo Luis Lepletier, Ailin Manarin, Romina Savino, Wilson Perez, Ana Rosa Bottasso, Oscar Adelmo |
author |
Villar, Silvina Raquel |
author_facet |
Villar, Silvina Raquel Ronco, Maria Teresa Fernandez Bussy, Rodrigo Roggero, Edgardo Luis Lepletier, Ailin Manarin, Romina Savino, Wilson Perez, Ana Rosa Bottasso, Oscar Adelmo |
author_role |
author |
author2 |
Ronco, Maria Teresa Fernandez Bussy, Rodrigo Roggero, Edgardo Luis Lepletier, Ailin Manarin, Romina Savino, Wilson Perez, Ana Rosa Bottasso, Oscar Adelmo |
author2_role |
author author author author author author author author |
dc.subject.none.fl_str_mv |
Glucocorticoides Factor de Necrosis tumoral Adrenales Trypanosoma cruzi |
topic |
Glucocorticoides Factor de Necrosis tumoral Adrenales Trypanosoma cruzi |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3 https://purl.org/becyt/ford/3.1 |
dc.description.none.fl_txt_mv |
Adrenal steroidogenesis is under a complex regulation involving extrinsic and intrinsic adrenal factors. TNF-a is an inflammatory cytokine produced in response to tissue injury and several other stimuli. We have previously demonstrated that TNF-R1 knockout (TNF-R12/2) mice have a dysregulated synthesis of glucocorticoids (GCs) during Trypanosoma cruzi acute infection. Since TNF-a may influence GCs production, not only through the hypothalamus-pituitary axis, but also at the adrenal level, we now investigated the role of this cytokine on the adrenal GCs production. Wild type (WT) and TNF-R12/2 mice undergoing acute infection (Tc-WT and Tc-TNF-R12/2 groups), displayed adrenal hyperplasia together with increased GCs levels. Notably, systemic ACTH remained unchanged in Tc-WT and Tc-TNF-R12/2 compared with uninfected mice, suggesting some degree of ACTH-independence of GCs synthesis. TNF-a expression was increased within the adrenal gland from both infected mouse groups, with Tc-WT mice showing an augmented TNF-R1 expression. Tc-WT mice showed increased levels of P-p38 and P-ERK compared to uninfected WT animals, whereas Tc-TNF-R12/2 mice had increased p38 and JNK phosphorylation respect to Tc-WT mice. Strikingly, adrenal NF-kB and AP-1 activation during infection was blunted in Tc-TNF-R12/2 mice. The accumulation of mRNAs for steroidogenic acute regulatory protein and cytochrome P450 were significantly increased in both Tc-WT and Tc-TNF-R12/2 mice; being much more augmented in the latter group, which also had remarkably increased GCs levels. TNF-a emerges as a potent modulator of steroidogenesis in adrenocortical cells during T. cruzi infection in which MAPK pathways, NF-kB and AP-1 seem to play a role in the adrenal synthesis of pro-inflammatory cytokines and enzymes regulating GCs synthesis. These results suggest the existence of an intrinsic immune-adrenal interaction involved in the dysregulated synthesis of GCs during murine Chagas disease. Fil: Villar, Silvina Raquel. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia; Fil: Ronco, Maria Teresa. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas; Fil: Fernandez Bussy, Rodrigo. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia; Fil: Roggero, Edgardo Luis. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia; Fil: Lepletier, Ailin. Ministerio de Salud de Brasil. Fundacion Oswaldo Cruz; Fil: Romina Manarin. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia; Fil: Savino, Wilson. Ministerio de Salud de Brasil. Fundacion Oswaldo Cruz; Fil: Perez, Ana Rosa. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia; Fil: Bottasso, Oscar Adelmo. Universidad Nacional de Rosario. Facultad de Cs.medicas. Instituto de Inmunologia; |
description |
Adrenal steroidogenesis is under a complex regulation involving extrinsic and intrinsic adrenal factors. TNF-a is an inflammatory cytokine produced in response to tissue injury and several other stimuli. We have previously demonstrated that TNF-R1 knockout (TNF-R12/2) mice have a dysregulated synthesis of glucocorticoids (GCs) during Trypanosoma cruzi acute infection. Since TNF-a may influence GCs production, not only through the hypothalamus-pituitary axis, but also at the adrenal level, we now investigated the role of this cytokine on the adrenal GCs production. Wild type (WT) and TNF-R12/2 mice undergoing acute infection (Tc-WT and Tc-TNF-R12/2 groups), displayed adrenal hyperplasia together with increased GCs levels. Notably, systemic ACTH remained unchanged in Tc-WT and Tc-TNF-R12/2 compared with uninfected mice, suggesting some degree of ACTH-independence of GCs synthesis. TNF-a expression was increased within the adrenal gland from both infected mouse groups, with Tc-WT mice showing an augmented TNF-R1 expression. Tc-WT mice showed increased levels of P-p38 and P-ERK compared to uninfected WT animals, whereas Tc-TNF-R12/2 mice had increased p38 and JNK phosphorylation respect to Tc-WT mice. Strikingly, adrenal NF-kB and AP-1 activation during infection was blunted in Tc-TNF-R12/2 mice. The accumulation of mRNAs for steroidogenic acute regulatory protein and cytochrome P450 were significantly increased in both Tc-WT and Tc-TNF-R12/2 mice; being much more augmented in the latter group, which also had remarkably increased GCs levels. TNF-a emerges as a potent modulator of steroidogenesis in adrenocortical cells during T. cruzi infection in which MAPK pathways, NF-kB and AP-1 seem to play a role in the adrenal synthesis of pro-inflammatory cytokines and enzymes regulating GCs synthesis. These results suggest the existence of an intrinsic immune-adrenal interaction involved in the dysregulated synthesis of GCs during murine Chagas disease. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-05-22 |
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/11336/511 Villar, Silvina Raquel; Ronco, Maria Teresa; Fernandez Bussy, Rodrigo; Roggero, Edgardo Luis; Lepletier, Ailin; Romina Manarin; Savino, Wilson ; Perez, Ana Rosa; Bottasso, Oscar Adelmo; Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1; Public Library Science; Plos One; 8; 5; 22-5-2013; 1-13; 1932-6203 |
url |
http://hdl.handle.net/11336/511 |
identifier_str_mv |
Villar, Silvina Raquel; Ronco, Maria Teresa; Fernandez Bussy, Rodrigo; Roggero, Edgardo Luis; Lepletier, Ailin; Romina Manarin; Savino, Wilson ; Perez, Ana Rosa; Bottasso, Oscar Adelmo; Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1; Public Library Science; Plos One; 8; 5; 22-5-2013; 1-13; 1932-6203 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0063814 |
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 |
Public Library Science |
publisher.none.fl_str_mv |
Public Library Science |
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_ |
1844613601991589888 |
score |
13.070432 |