Tumor Necrosis Factor-α Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1

Adrenal steroidogenesis is under a complex regulation involving extrinsic and intrinsic adrenal factors. TNF-α is an inflammatory cytokine produced in response to tissue injury and several other stimuli. We have previously demonstrated that TNF-R1 knockout (TNF-R1−/−) mice have a dysregulated synthe...

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Autores principales: Villar, Silvina Raquel, Ronco, María Teresa, Fernández Bussy, Rodrigo, Roggero, Eduardo, Lepletier, Ailin, Manarin, Romina, Savino, Wilson, Pérez, Ana Rosa, Bottasso, Oscar
Formato: artículo article publishedVersion
Lenguaje:Inglés
Publicado: PLOS (Public Library of Science) 2014
Materias:
Trypanosoma cruzi
Parasitic diseases
MAPK signaling cascades
Inflammation
Adrenal glands
Cytokines
Enzyme regulation
Gene expression
Acceso en línea:http://hdl.handle.net/2133/3081
http://hdl.handle.net/2133/3081
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-3081
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv en
topic Trypanosoma cruzi
Parasitic diseases
MAPK signaling cascades
Inflammation
Adrenal glands
Cytokines
Enzyme regulation
Gene expression
spellingShingle Trypanosoma cruzi
Parasitic diseases
MAPK signaling cascades
Inflammation
Adrenal glands
Cytokines
Enzyme regulation
Gene expression
Villar, Silvina Raquel
Ronco, María Teresa
Fernández Bussy, Rodrigo
Roggero, Eduardo
Lepletier, Ailin
Manarin, Romina
Savino, Wilson
Pérez, Ana Rosa
Bottasso, Oscar
Tumor Necrosis Factor-α Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1
topic_facet Trypanosoma cruzi
Parasitic diseases
MAPK signaling cascades
Inflammation
Adrenal glands
Cytokines
Enzyme regulation
Gene expression
description Adrenal steroidogenesis is under a complex regulation involving extrinsic and intrinsic adrenal factors. TNF-α is an inflammatory cytokine produced in response to tissue injury and several other stimuli. We have previously demonstrated that TNF-R1 knockout (TNF-R1−/−) mice have a dysregulated synthesis of glucocorticoids (GCs) during Trypanosoma cruzi acute infection. Since TNF-α 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-R1−/− mice undergoing acute infection (Tc-WT and Tc-TNF-R1−/− groups), displayed adrenal hyperplasia together with increased GCs levels. Notably, systemic ACTH remained unchanged in Tc-WT and Tc-TNF-R1−/− compared with uninfected mice, suggesting some degree of ACTH-independence of GCs synthesis. TNF-α 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-R1−/− mice had increased p38 and JNK phosphorylation respect to Tc-WT mice. Strikingly, adrenal NF-κB and AP-1 activation during infection was blunted in Tc-TNF-R1−/− mice. The accumulation of mRNAs for steroidogenic acute regulatory protein and cytochrome P450 were significantly increased in both Tc-WT and Tc-TNF-R1−/− mice; being much more augmented in the latter group, which also had remarkably increased GCs levels. TNF-α emerges as a potent modulator of steroidogenesis in adrenocortical cells during T. cruzi infection in which MAPK pathways, NF-κB 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.
format artículo
article
publishedVersion
author Villar, Silvina Raquel
Ronco, María Teresa
Fernández Bussy, Rodrigo
Roggero, Eduardo
Lepletier, Ailin
Manarin, Romina
Savino, Wilson
Pérez, Ana Rosa
Bottasso, Oscar
author_facet Villar, Silvina Raquel
Ronco, María Teresa
Fernández Bussy, Rodrigo
Roggero, Eduardo
Lepletier, Ailin
Manarin, Romina
Savino, Wilson
Pérez, Ana Rosa
Bottasso, Oscar
author_sort Villar, Silvina Raquel
title Tumor Necrosis Factor-α Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1
title_short Tumor Necrosis Factor-α Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1
title_full Tumor Necrosis Factor-α Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1
title_fullStr Tumor Necrosis Factor-α Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1
title_full_unstemmed Tumor Necrosis Factor-α Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1
title_sort tumor necrosis factor-α regulates glucocorticoid synthesis in the adrenal glands of trypanosoma cruzi acutely-infected mice. the role of tnf-r1
publisher PLOS (Public Library of Science)
publishDate 2014
url http://hdl.handle.net/2133/3081
http://hdl.handle.net/2133/3081
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