Examinando por Autor "Fernández Bussy, Rodrigo"

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    Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment
    (PLoS, 2016-01) González, Florencia Belén; Calmon-Hamaty, Flavia; Cordeiro, Synara Nô Seara; Fernández Bussy, Rodrigo; Spinelli, Silvana Virginia; D'Attilio, Luciano; Bottasso, Oscar; Savino, Wilson; Cotta-de-Almeida, Vinícius; Raquel Villar, Silvina; Pérez, Ana Rosa
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    ÍtemAcceso Abierto
    Tumor Necrosis Factor-α Regulates Glucocorticoid Synthesis in the Adrenal Glands of Trypanosoma cruzi Acutely-Infected Mice. The Role of TNF-R1
    (PLOS (Public Library of Science), 2013-05-22) Villar, Silvina Raquel; Ronco, María Teresa; Fernández Bussy, Rodrigo; Roggero, Eduardo; Lepletier, Ailin; Manarin, Romina; Savino, Wilson; Pérez, Ana Rosa; Bottasso, Oscar
    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.