| Author | Villar, Silvina R. | |
| Author | Ronco, M. Teresa | |
| Author | Fernández Bussy, Rodrigo | |
| Author | Roggero, Eduardo | |
| Author | Lepletier, Ailin | |
| Author | Manarin, Romina | |
| Author | Savino, Wilson | |
| Author | Pérez, Ana Rosa | |
| Author | Bottasso, Oscar | |
| Access date | 2016-07-21T13:50:55Z | |
| Available date | 2016-07-21T13:50:55Z | |
| Document date | 2013 | |
| 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. | pt_BR |
| ISSN | 1932-6203 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/15031 | |
| Language | eng | pt_BR |
| Publisher | Public Library of Science | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Glucocorticoides | pt_BR |
| Subject in Portuguese | Doença de Chagas | pt_BR |
| Subject in Portuguese | Necrose tumoral | pt_BR |
| Subject in Portuguese | Glândulas supra-renais | pt_BR |
| Title | Tumor necrosis factor-α regulates glucocorticoid synthesis in the adrenal glands of Trypanosoma cruzi acutely-infected mice. the role of TNF-R1 | pt_BR |
| Type | Article | |
| DOI | 10.1371/journal.pone.0063814 | |
| 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. | pt_BR |
| Affilliation | Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología. Rosario, Argentina. | pt_BR |
| Affilliation | Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental (IFISE-CONICET). Rosario, Argentina.) | pt_BR |
| Affilliation | Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología. Rosario, Argentina. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología. Rosario, Argentina. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología. Rosario, Argentina. | pt_BR |
| Affilliation | Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología. Rosario, Argentina. | pt_BR |
| Subject | Trypanosoma cruzi | pt_BR |
| Subject | Tumor Necrosis | pt_BR |
| Subject | Glucocorticoid Synthesis | pt_BR |
| Subject | Adrenal Glands | pt_BR |
| Subject | Chagas disease | pt_BR |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
