Role of PPARs in Trypanosoma cruzi Infection: Implications for Chagas Disease Therapy

Figure 2

Anti-inflammatory actions of 15dPGJ2 in T. cruzi-infected cardiomyocytes. 15dPGJ2 can exert its effects by binding to PPAR-γ or through interaction with intracellular targets like NF-κB-signaling pathway and Erk MAP kinase cascade. By PPAR-γ-dependent mechanisms, the 15dPGJ2-PPAR-γ complex forms a heterodimer with nuclear retinoid X receptor (RXR) to recognize PPAR-response elements (PPREs) in the promoter region of the target genes thereby stimulating their transcription. In the cytosol, 15dPGJ2 can also bind specific residues in IKK, p50, or p65 of the NF-κB-signaling pathway, or MEK1/2 and Erk1/2 in the MAP kinase pathway leading to functional inactivation of inflammatory target genes. The consequent inhibition of inflammatory factors/mediators by 15dPGJ2 promotes an increase in the number of intracellular parasites.