(FBIOyF) Departamento de Ciencias Fisiológicas

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https://rephip.unr.edu.ar/handle/2133/8552

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Examinando (FBIOyF) Departamento de Ciencias Fisiológicas por Autor "Bottasso, Oscar"

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  • Miniatura
    ÍtemAcceso Abierto
    Studies on the contribution of PPAR Gamma to tuberculosis physiopathology
    (Frontiers Media, 2023-04-28) Díaz, Ariana; D’Attilio, Luciano David; Penas, Federico; Bongiovanni, Bettina; Massa, Estefania; Cevey, Agata; Santucci, Natalia; Bottasso, Oscar; Goren, Nora; Bay, María Luisa
    Introduction: Tuberculosis (TB) is a major health problem characterized by an immuno-endocrine imbalance: elevated plasma levels of cortisol and pro- and anti-in fl ammatory mediators, as well as reduced levels of dehydroepiandrosterone. The etiological agent, Mycobacterium tuberculosis (Mtb), is captured by pulmonary macrophages (Mf), whose activation is necessary to cope with the control of Mtb, however, excessive activation of the inflammatory response also leads to tissue damage. Glucocorticoids (GC) are critical elements to counteract the immunoinflammatory reaction, and peroxisome proliferator-activated receptors (PPARs) are also involved in this regard. The primary forms of these receptors are PPARϒ, PPARa, and PPARb/d, the former being the most involved in anti-inflammatory responses. In this work, we seek to gain some insight into the contribution of PPARϒ in immunoendocrine-metabolic interactions by focusing on clinical studies in pulmonary TB patients and in vitro experiments on a Mf cell line. Methods and results: We found that TB patients, at the time of diagnosis, showed increased expression of the PPARϒ transcript in their peripheral blood mononuclear cells, positively associated with circulating cortisol and related to disease severity. Given this background, we investigated the expression of PPARϒ (RT-qPCR) in radiation-killed Mtb-stimulated human Mf. The Mtb stimulation of Mf derived from the human line THP1 significantly increased the expression of PPARϒ, while the activation of this receptor by a specific agonist decreased the expression of pro- and anti-inflammatory cytokines (IL-1β and IL-10). As expected, the addition of GC to stimulated cultures reduced IL-1β production, while cortisol treatment together with the PPARϒ agonist lowered the levels of this proinflammatory cytokine in stimulated cultures. The addition of RU486, a glucocorticoid receptor antagonist, only reversed the inhibition produced by the addition of GC. Conclusion: The current results provide a stimulating background for further analysis of the interconnection between PPARs and steroid hormones in the context of Mtb infection.
  • Miniatura
    ÍtemAcceso Abierto
    The immunoregulatory actions of DHEA in tuberculosis, a tool for therapeutic intervention?
    (Frontiers Media, 2022-06-06) Bongiovanni, Bettina; Díaz, Ariana; Santucci, Natalia; D’Attilio, Luciano David; Bottasso, Oscar; Hernández-Pando, Rogelio; Bay, María Luisa
    Dehydroepiandrosterone (DHEA) is an androgen synthesized by the adrenal cortex, which is an intermediary in the biosynthesis of sex hormones, such as testosterone and estradiol. DHEA mostly circulates as a conjugated ester, in the form of sulfate (DHEAS). There exist several endogenous factors able to influence its synthesis, the most common ones being the corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH), growth factors, and proinflammatory cytokines, among others. Like other steroid hormones, DHEA, can alter the functioning of immune cells and therefore the course of diseases exhibiting an immune-inflammatory component, mostly from autoimmune or infectious nature. We herein review the role played by DHEA during a major infectious disease like tuberculosis (TB). Data recorded from TB patients, mouse models, or in vitro studies show that DHEA is likely to be implied in better disease control. This provides a stimulating background for carrying out clinical studies aimed at assessing the usefulness of DHEA as an adjuvant in TB patients.