Proinflammatory cytokines and EPAC2 as possible modulators of adrenal sterodogenesis during experimental Trypanososma cruzi infection

DE MEIS J.; GONZÁLEZ F.; DE FRIAS CARVALHO V.; INSUELA DBR.; ROGGERO E.; PEREZ AR.; BOTTASSO O.; VILLAR S.

Bs As

Congreso; 1st LASID SAI FAIC Meeting; 2015

Sociedad Brasilera de Inmunologia

The hypothalamus-pituitary-adrenal axis is activated during inflammatory or infectious states by cytokines, such as IL-1b and TNF-a In the adrenal cortex, the biosynthesis of glucocorticoids (GC) is primarily regulated by ACTH through PKA-dependent signaling pathways. Beyond this system, pro-inflammatory cytokines and Exchange Protein directly Activated by cAMP 2 (Epac2) can also take part directly in the adrenal release of GC. Previous studies in mice infected withTrypanosoma cruzi (Tc) showed increased circulating levels of pro-inflammatory cytokines and GC without changes in serum ACTH. Given this background, we studied the intra-adrenal expression of proinflammatory cytokines together with Epac2 protein contents, because of their potential modulatory roleson GC synthesis. C57BL/6 mice were infected with Tc or inoculated with saline (Co). Assessments were made at day 17 post-infection. Infected mice had a cortical hypertrophy and overexpression of ACTH receptor (immunohystochemistry) respect Co. Real time PCR for pro-inflammatory cytokines showed increased adrenal levels of TNF-a and IL-1b [TNF-a= Co:5.1±0.8, Tc:57±4.5, IL-1b =Co:26.8±6.2, Tc:55.9±7.4, p