PRO-INFLAMMATORY CYTOKINES AND EPAC2 AS POSSIBLE MODULATORS OF ADRENAL STEROIDOGENESIS DURING EXPERIMENTAL TRYPANOSOMA CRUZI INFECTION

SILVINA VILLAR; EDUARDO ROGGERO1, FLAVIA LAMBERTUCCI2, DA SILVA OLIVEIRA BARBOSA1, ESDRAS, FLORENCIA GONZÁLEZ1, VINICIUS DE FRIAS CARVALHO4, JULIANA DE MEIS3, OSCAR BOTTASSO1, M. TERESA RONCO2, ANA R PÉREZ1

Congreso; Reunion Conjunta de Sociedades de Biociencia; 2018

During inflammatory or infectious stress, the HPA axis is activated byimmune mediators. Adrenal steroidogenesis is a dynamic process, under thestimulation of ACTH, this process, depends on the activation of signaling pathways particularly mediated by PKA. However, glucocorticoid (GC) synthesis can be stimulated by cytokines and Exchange Protein directly Activated by cAMP 2(Epac2) troughs PKA-independent pathway. Previous studies in mice infected with Trypanosoma cruzi (Tc) showed increasedcirculating levels of GC without changes in ACTH at 17days post-infection (dpi), while an increase of intra-adrenal expression of pro-inflammatory cytokines was observed. In this study, we determined at different dpi the expression of PKA/PKAp (asa measure of ACTH-pathway activation), IL-1receptor (IL-1R) and Epac2 (as a potential modulator of adrenal steroideogénesis).C57BL/6 mice were infected with Tc or inoculated with saline (Co). Data areshowed as mean±SEM (n=3-5/day/group). Assessments were made between 10 to 16 dpi.IL-1β is increased in plasma during infection [IL-1β (ELISA, pg/ml); Co:22.7±9.0,Tc(11dpi):59±34.6*, Tc(16dpi):82.13±27.2*, *p<0.05 vs Co]. The PKA/PKAp ratio  was increased at 11 dpi [Western blot, PKA/PKAp: Co=1±01;Tc(10dpi)=1.1±0.1; Tc(11dpi)=2.4±0.7*; Tc(12dpi)=0.8±0.5; Tc(13dpi)=1.0±0.2;Tc(14dpi)=1.1±0.2; Tc(15dpi)=0.9±0.2; Tc(16dpi)=0.8±0.1; *p<0,05 vs Co]. Tc mice displayed an intra-adrenalelevation of Epac2 after 14dpi (p<0,05 vs Co), decreasing after 16dpi.  In parallel, the expression levels of IL-1R startto increase from 13dpi (Western blot, p<0,05). Tc infection activates the steroidogenicsynthesis which results in remarkably increased GC production. Our results suggest that atthe beginning, GC secretion may be increase by the ACTH-mediatedresponse, but in a late phase of infection, GC secretion might be maintained byother mediators including IL-1 and Epac2.