INSTITUTO DE INVESTIGACIONES EN MICROBIOLOGIA Y PARASITOLOGIA MEDICA
Unidad Ejecutora - UE
PPARg ligand treatment inhibits cardiac inflammatory mediators in both acute and chronic mouse models of Trypanosoma cruzi infection
PENAS, F; MIRKIN, GA; HOVSEPIAN, E; CEVEY, A; CACURRI, R; SALES, ME; GOREN,NB
BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE
ELSEVIER SCIENCE BV
Lugar: Amsterdam; Año: 2013 vol. 1832 p. 239 - 239
Trypanosoma cruzi (T. cruzi), the etiological agent of Chagas´ disease, causes cardiac alterations in the host. Although the main clinical manifestations arise during the chronic stage, the mechanisms leading to heart damage develop early during infection. In fact, an intense inflammatory response is observed from acute stage of infection. Recently, peroxisome proliferator-activated receptors (PPARs) have attracted research interest due to their participation in the modulation of inflammation. In this work we addressed the role of 15-Deoxy-∆12,14 PGJ2 (15dPGJ2), a PPARã natural ligand in the regulation of inflammatory mediators, in acute and chronic experimental mouse models of Chagas´ disease with the RA and K98 T. cruzi strains, respectively. This work demonstrates that 15dPGJ2 treatment inhibits the expression and activity of inducible nitric oxide synthase (NOS2) as well as TNF-á and IL-6 mRNA levels. Also, expression and activity of metalloproteinases 2 (MMP-2) and 9 (MMP9) were inhibited by 15dPGJ2. Moreover GW9662, a specific PPARã antagonist, revealed the participation of other signaling pathways since, in GW9662 presence, 15dPJG2 had a partial effect on the inhibition of inflammatory parameters in the acute model of infection. Accordingly, NF-êB activation was demonstrated, assessing p65 nuclear translocation in the hearts of infected mice with both T. cruzi strains. Such effect was inhibited after 15dPGJ2 treatment. Our findings support the concept that in vivo PPARã and NF-êB pathways are implicated in the inhibitory effects of 15dPGJ2 on inflammatory mediators at different times depending on whether the infection is caused by the lethal or non-lethal T. cruzi strain.