Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/15031
Title: Tumor necrosis factor-α regulates glucocorticoid synthesis in the adrenal glands of Trypanosoma cruzi acutely-infected mice. the role of TNF-R1
Authors: Villar, Silvina R.
Ronco, M. Teresa
Fernández Bussy, Rodrigo
Roggero, Eduardo
Lepletier, Ailin
Manarin, Romina
Savino, Wilson
Pérez, Ana Rosa
Bottasso, Oscar
Affilliation: Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología. Rosario, Argentina.
Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental (IFISE-CONICET). Rosario, Argentina.)
Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología. Rosario, Argentina.
Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología. Rosario, Argentina / Universidad Abierta Interamericana (U.A.I.). Facultad de Medicina. Departamento de Fiisiologia. Rosario, Argentina.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología. Rosario, Argentina.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología. Rosario, Argentina.
Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología. Rosario, Argentina.
Abstract: 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.
Keywords: Trypanosoma cruzi
Tumor Necrosis
Glucocorticoid Synthesis
Adrenal Glands
Chagas disease
keywords: Trypanosoma cruzi
Glucocorticoides
Doença de Chagas
Necrose tumoral
Glândulas supra-renais
Issue Date: 2013
Publisher: Public Library of Science
Citation: VILLAR, Silvina R. et al. Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1. Plos One, v.8, n.5, e63814, 13p, May 2013.
DOI: 10.1371/journal.pone.0063814
ISSN: 1932-6203
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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