Role of PI3K pathway in the anti-inflammatory effect of Benznidazole

SEQUEYRA, ALDANA; RADA, MARÍA JIMENA; CEVEY, ÀGATA CAROLINA; COMITO, ROCIO; MIRKIN, GERARDO A.; PIERALISI, AZUL VICTORIA; PENAS, FEDERICO NICOLÁS; GOREN, NORA BEATRIZ

Mar del Plata

Congreso; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2019

Sociedad Argentina de Investigación Clínica

Chagas disease is the main cause of dilated cardiomyopathy in Latin America. During acute infection, the inflammatory response is critical for the control of parasite proliferation and its evolution. Benznidazole, one of the antiparasitic drugs currently used for its treatment, also exerts anti-inflammatory effects. We have previously described that benznidazole inhibits the activation of the NF-κB pathway by increasing the expression of SOCS3 through the IL-10 / STAT3 / SOCS3 axis.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. To assess the anti-inflammatory effect of benznidazole, regardless of its antiparasitic, heart cells were stimulated with 10 μg / ml of LPS and pretreated with 15 μM of benznidazole. In parallel, the treatments were performed 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