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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/511

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network_name_str CONICET Digital (CONICET)
spelling 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
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