Pro-inflammatory cytokines and EPAC2 as possible modulators of adrenal steroidogenesis during experimental Trypanosoma cruzi infection

EDUARDO ROGGERO; FLORENCIA GONZALEZ; MARIA TERESA RONCO; FLAVIA LAMBERTUCCI; OSCAR BOTTASSO; SILVINA VILLAR; ESDRAS DA SILVA OLIVEIRA BARBOSA; VINICIUS DE FRIAS CARVALHO; ANA ROSA PÉREZ

Buenos Aires

Congreso; Reunión conjunta de Sociedades de Biociencias y 65ta Reunión de la SAI; Buenos Aires, 13-17 Noviembre 2017; 2017

Reunión Conjunta de Sociedades de Biociencia

During inflammatory or infectious stress, the HPA axis is activated by immune mediators. Adrenal steroidogenesis is a dynamic process. While ACTH stimulation leads to the activation of signaling pathways particularly mediated by PKA, glucocorticoid (GC) synthesis can be also stimulated by cytokines and Exchange Protein directly Activated by cAMP 2 (Epac2) through a PKA-independent pathway. Previous studies in mice infected with Trypanosoma cruzi (Tc) showed increased circulating levels of GC without changes in ACTH at 17 days post-infection (dpi), in presence of an increased intra-adrenal expression of pro-inflammatory cytokines. Extending these findings, Tc-infected mice were analyzed at different dpi for the expression of PKA/PKAp (as a measure of the ACTH-pathway activation), IL-1 receptor (IL-1R) and Epac2 (as a potential modulator of adrenal steroideogénesis). C57BL/6 mice were infected with Tc or inoculated with saline (Co). Assessments were performed between 10 to 16 dpi and data were presented as means ± SEM (n=3-5/day/group). Plasma IL-1β (ELISA) was increased during infection [pg/ml; Co:22.7±9.0, Tc (11dpi): 59±34.6*, Tc (16dpi): 82.13±27.2*, *p