Role of PI3K pathway in the antiinflammatory effect of benznidazole

PIERALISI, AZUL VICTORIA; FEDERICO NICOLÁS PENAS; GOREN, NORA; ÁGATA CAROLINA CEVEY; COMITO ROCIO; GERARDO ARIEL MIRKIN; SEQUEYRA ALDANA; MARÍA JIMENA RADA

Mar del Plata

Congreso; Reunión Anual De Sociedades De Biociencia 2019; 2019

Sociedad Argentina de Investigación Clínica (SAIC)

Chagas disease is the main cause of dilated cardiomyopathy in Latin America. During the acute infection, the inflammatory response is critical for the control of parasite proliferation and disease evolution. Benznidazole, one of the antiparasitic drugs currently used for its treatment, also exerts anti-inflammatory effects. Previously, we described that benznidazole inhibits the activation of the NF-kappaB pathway by increasing the expression of SOCS3 through the IL-10/STAT3/SOCS3 pathway. It has been reported that PI3K is a negative regulator of inflammation, partly through SOCS3. To deepen the knowledge of the mechanism of action of benznidazole, we used a primary culture of mouse neonatal cardiomyocytes. Heart cells were pretreated with 15 µM of benznidazole and then stimulated with 10 µg/ml of LPS, to assess the anti-inflammatory effect of benznidazole, regardless of its antiparasitic effect. The treatments were performed, in parallel, in the presence of LY294002, a specific inhibitor of PI3K activity. Under these conditions, we found that benznidazole could not increase SOCS3 after 24 h of stimulation, evaluated by RT-qPCR (p