Apoptosis signaling pathways in adrenal glands during experimental Trypanosoma cruzi infection

VILLAR S; MARTINELLI R; GONZALEZ F; ROGGERO E; PEREZ A; RONCO T; BOTTASSO O

Mar del Plata

Congreso; LIX Reunión Científica Anual de la SAIC, Mar del Plata 19-22 Noviembre de 2014; 2014

Sociedad Argentina de Investigación Clínica

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-kB 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-kB pathways regulate the expression of enzymes involved in GC synthesis. Now we aimed to evaluate whether TNFa 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