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

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dc.contributor.author Villar, Silvina Raquel
dc.contributor.author Ronco, María Teresa
dc.contributor.author Fernández Bussy, Rodrigo
dc.contributor.author Roggero, Eduardo
dc.contributor.author Lepletier, Ailin
dc.contributor.author Manarin, Romina
dc.contributor.author Savino, Wilson
dc.contributor.author Pérez, Ana Rosa
dc.contributor.author Bottasso, Oscar
dc.date.accessioned 2014-03-26T19:33:41Z
dc.date.available 2014-03-26T19:33:41Z
dc.date.issued 2013-05-22
dc.identifier.citation Villar SR, Ronco MT, Ferna´ndez Bussy R, Roggero E, Lepletier A, et al. (2013) Tumor Necrosis Factor-a Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1. PLoS ONE 8(5): e63814. doi:10.1371/journal.pone.0063814 es
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/2133/3081
dc.description.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. es
dc.format application/pdf
dc.language.iso en es
dc.publisher PLOS (Public Library of Science) es
dc.rights openAccess
dc.subject Trypanosoma cruzi es
dc.subject Parasitic diseases es
dc.subject MAPK signaling cascades es
dc.subject Inflammation es
dc.subject Adrenal glands es
dc.subject Cytokines es
dc.subject Enzyme regulation es
dc.subject Gene expression es
dc.title Tumor Necrosis Factor-α Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1 es
dc.type artículo
dc.type article
dc.type publishedVersion
dc.description.peerreviewed Peer reviewed es
dc.relation.publisherversion http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0063814 es
dc.description.affiliation Fil. Villar, Silvina R. Instituto de Inmunología, Facultad de Ciencias Médicas, Universidad Nacional de Rosario; Argentina
dc.description.affiliation Fil. Ronco, María Teresa. Instituto de Fisiología Experimental (IFISE-CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario; Argentina

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