Evaluation of the activity of macrophage FABP4 inhibitors in Leishmania infections

Abstract

The fatty acid-binding protein type 4 (FABP4) is present in the cytosol of macrophages and adipocytes and participate in the fatty acids traffic to different cellular compartments. The investigation of its role in the course of Leishmania infection is the main objective of the project 14 / 21129-4, supported by FAPESP. Initially, the toxicity profile of two specific inhibitors of FABP4 activity will be determined using: i) bone marrow derived macrophages from BALB/c mice; ii) promastigote cultures for three important species of Leishmania in Brazil: Leishmania (Leishmania) infantum chagasi, L. (L.) amazonensis and L. (V.) braziliensis. Optimal ranges of concentrations for each of these inhibitors will be calculated for further evaluation of the activity of the inhibitors in Leishmania-infected macrophages after 24, 48 and 72 hours. Results will be presented as inhibitory concentrations for 50 and 90% cell viability (CC50%; EC50%; EC90%), and infectivity index (total percentage of macrophage infection and the number of amastigotes per macrophage). This initial work will expand our comprehension on the role of FABP4 in the infective process of different Leishmania species when residing in host cells.