PRO-INFLAMMATOY CYTOKINES AND EPAC2 AS POSSIBLE MODULATORS OF ADRENAL STEROIDOGENESIS DURIGN EXPERIMENTAL TRYPANOSOMA CRUZI INFECTION

JULIANA DE MEIS ; FLORENCIA GONZÁLEZ; VINICIUS DE FRIAS CARVALHO; DANIELLA BR INSUELA; EDUARDO ROGGERO; ANA R PÉREZ; OSCAR BOTTASSO; SILVINA R VILLAR

Buenos Aires

Congreso; IV LASI Meeting, LVIII Argentininean Immunology Society Meeting and II French-Argentine Immunology Meeting; 2015

The hypothalamus-pituitary-adrenal axis isactivated during inflammatory or infectious states by cytokines,such as IL-1βand TNF-α.In the adrenal cortex, the biosynthesis of glucocorticoids (GC) is primarily regulatedby ACTH through PKA-dependent signaling pathways. Beyond this system,pro-inflammatory cytokines and ExchangeProtein directly Activated by cAMP 2 (Epac2) can also take part directly in the adrenal release of GC. Previousstudies in mice infected with Trypanosomacruzi (Tc) showed increased circulating levels of pro-inflammatory cytokines and GC without changesin serum ACTH. Given this background, we studied the intra-adrenalexpression of pro-inflammatory cytokines together with Epac2 protein contents, because of their potential modulatory roles on GC synthesis. C57BL/6 mice were infected with Tc orinoculated with saline (Co). Assessments were made at day 17 post-infection. Infectedmice had a cortical hypertrophyand overexpression of ACTH receptor (immunohystochemistry) respect Co. Real time PCR for pro-inflammatorycytokines showed increased adrenal levels of TNF-α and IL-1β [ΔCt, TNF-α=Co:5.1±0.8, Tc:57±4.5, IL-1β = Co:26.8±6.2, Tc:55.9±7.4, p<0.05 both cases],without changes in IL-6. The expression of enzymes driving GC synthesis wasincreased during infection [Real Time RT-PCR, ΔCt; i.e.: StAR= Co:346±118;Tc:2740±195 p<0.05]. Tc mice alsodisplayed increased Epac2 contents in the adrenal gland respect Co mice (Westernblot; Epac2=Co:100±45; Tc:1539±572 p<0,05). Data: mean±SEM(n=3-5/day/group). Infection with Tcactivates genes coding for steroidogenic proteins which results in remarkablyincreased GC production. Such over-stimulation in GC synthesis seems to be locallymediated by pro-inflammatory cytokines and the Epac2 signaling pathway.