ROLE OF P110δ CATALYTIC SUBUNIT OF THE CLASS IA ISOFORM OF PI3K IN THE ANTI-INFLAMMATORY EFFECT OF BENZNIDAZOLE

MASCOLO P.; CEVEY Á; PIERALISI, AZUL VICTORIA; SEQUEYRA ALDANA; PENAS F; MIRKIN G.,; GOREN, NORA

Buenos Aires

Congreso; Reunión Anual De Sociedades de Biociencia 2020; 2020

Sociedad Argentina de Investigación Clínica (SAIC), SAI, SAFIS

Benznidazole (Bz) is the drug-of-choice in many countries for thetreatment of Chagas Disease. Although it has been used in clinicalsettings for a long time, its mechanisms of action have not been fullyelucidated yet. Indeed, there is a general premise that the etiologicaltreatment contributes to a reduction of the parasite load and tofit the host immune response, leading to a balanced inflammatoryresponse which is crucial to control Chagas disease morbidity. Inaddition to its parasiticidal effect, we have previously reported thatBz inhibits the activation of the NF-κB pathway by increasing the expressionof SOCS3 through the IL-10/STAT3/SOCS3 pathway. Furthermore,in preliminary results, we showed that PI3K participatesin this effect in cardiac cells. In this work, we assessed this issuein a macrophage (Mф) cell line (RAW 264.7). Mф were pre-treatedwith 15uM Bz and stimulated with 10 μg/ml of LPS. The treatmentswere performed, in parallel, in the presence of LY294002, aspecific inhibitor of PI3K activity. To deepen the knowledge of themechanism of action, we also used CAL-101, a specific inhibitor ofthe p110δ catalytic subunit of the Class IA isoform of PI3K. Inhibitionwas confirmed by the absence of phosphorylation of P70S6K(p