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

MASCOLO, PAULA; SEQUEYRA, ALDANA; GOREN, NORA BEATRIZ; CEVEY, ÀGATA CAROLINA; PENAS, FEDERICO NICOLÁS; PIERALISI, AZUL VICTORIA; MIRKIN, GERARDO A.

Buenos Aires (online)

Congreso; Reunión Anual de Sociedades de Biociencia 2020. SAIC-SAI-SAFIS; 2020

Sociedad Argentina de Investigación Clínica

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 etiological treatment 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 expression of 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-treated with 15uM Bz and stimulated with 10 µg/ml of LPS. The treatments were 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. Inhibition was confirmed by the absence of phosphorylation of P70S6K(p