APOPTOSIS SIGNALING PATHWAYS IN ADRENAL GLANDS DURING EXPERIMENTAL TRYPANOSOMA CRUZI INFECTION

SILVINA R VILLAR1, ROMINA MARTINELLI1, FLORENCIA GONZALEZ1, EDUARDO ROGGERO1, ANA R PEREZ1, M. RONCO2, OSCAR BOTTASSO1.

Mar del Plata

Congreso; LXII REUNION ANUAL Sociedad Argentina de Inmunología; 2014

TNFR1 and Fas share an intracellular domain crucial to induce apoptosis by triggering the initiator caspase-8 and subsequently the effector caspase 3; or could induce pathways that are involved in the inflammatory response including NF-êB and MAPK pathways. At adrenal level both pathways might influence glucocorticoid (GC) synthesis during an inflammatory process. We previously showed that during T. cruzi (Tc) infection MAPK and NF-êB pathways regulate the expression of enzymes involved in GC synthesis. Now we aimed to evaluate whether TNFá and FasL participate through their respective death receptors on adrenal cell apoptosis. We studied this issue infected with Tc C57BL/6 mice (B6) and mice deficient in TNFR1 (R1) and Fas (lpr mice). Controls were inoculated with saline solution (Co). Data was obtained at day 17 post-infection and expressed as mean ± SEM (n=5/group).  Histological evaluations showed increased values of adrenal apoptotic index (AI) in all infected groups, despite Tc-lpr displayed a minor AI compared withTc-B6 and Tc-R1 (AI%; number of apoptotic bodies/total cell number x 100); Tc-B6: 5.0±0.4*; Tc-R1: 5.0±0.5*; Tc-lpr: 1.2±0.2*#&. Caspase 8 activity was enhanced in Tc-B6 group compared to Tc-R1 and Tc-lpr mice (Relative activity; Tc-B6/Co-B6: 0.85±0.07, Tc-R1/Co-R1:0.60±0.08#, Tc-lpr/Co-lpr: 0.68±0.07#). Caspase 3 activity was augmented in all infected groups compared to their respective Co group (p<0.05), but without differences between infected ones. Adrenal lipoperoxidation (LP) were also evaluated as a signal of oxidative stress-induced apoptosis by HPLC. LP was only observed in the Tc-R1 group. In addition, Bax expression was diminished in Tc-lpr compared to the rest of infected mice (p<0,05). *p<0.05 vs uninfected counterparts, #p<0.05 vs Tc-WT, &p<0.05 vs R1. Our results showed that adrenal apoptosis are mainly triggered by Fas pathway. In R1 mice the results suggest that mechanisms inducing LP triggered apoptosis during infection.