HP24, a novel peroxisome proliferator activated receptor gamma agonist: molecular modeling and signaling pathways involved in T. cruzi-infected macrophages

PENAS, F; MIRKIN, GA; FERLIN, MG; CARTA, D; CEVEY, A; SALES, ME; MODENUTTI, C; RADA, J; GOREN,NB

C.A.B.A.

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

SAIC SAI SAP SAIB

T. cruzi infection induces an intense inflammatory response in diverse host tissues. Upon parasite uptake, macrophages, which are involved in the clearance of infection, increase inflammatory mediators, leading to parasite killing. However, exacerbation of the inflammatory response may lead to tissue damage. PPARγ is a ligand-dependent nuclear transcription factor that exerts important anti-inflammatory effects. In this work we show for the first time, the mechanism of action of a newly synthesized PPARγ ligand, pyridine carboxylic acid derivative (HP24) on macrophages (MΦ) from T. cruzi-infected mice. In order to elucidate how HP24 interacts with PPARγ, virtual docking analysis was performed. Then, we evaluated the signaling pathways involved in the action of HP24, using NO release as a functional marker. T0070907 (T007), a specific PPARγ antagonist, partially restored NO release by HP24-treated MΦ (P