SB-431542, a transforming growth factor beta inhibitor, impairs Trypanosoma cruzi infection in cardiomyocytes and parasite cycle completion.
The antiinflammatory cytokine transforming growth factor beta (TGF-beta) plays an important role in Chagas disease, a parasitic infection caused by the protozoan Trypanosoma cruzi. In the present study, we show that SB-431542, an inhibitor of the TGF-beta type I receptor (ALK5), inhibits T. cruzi-induced activation of the TGF-beta pathway in epithelial cells and in cardiomyocytes. Further, we demonstrate that addition of SB-431542 greatly reduces cardiomyocyte invasion by T. cruzi. Finally, SB-431542 treatment significantly reduces the number of parasites per infected cell and trypomastigote differentiation and release. Taken together, these data further confirm the major role of the TGF-beta signaling pathway in both T. cruzi infection and T. cruzi cell cycle completion. Our present data demonstrate that small inhibitors of the TGF-beta signaling pathway might be potential pharmacological tools for the treatment of Chagas disease.
Waghabi
Mariana C
MC
Laboratorio de Genômica Funcional e Bioinformática, Departamento de Bioquímica e Biologia Molecular, Instituto Oswaldo Cruz, Brasil, Rio de Janeiro, RJ, Brazil.
Keramidas
Michelle
M
Calvet
Claudia M
CM
Meuser
Marcos
M
de Nazaré C Soeiro
Maria
M
Mendonça-Lima
Leila
L
Araújo-Jorge
Tania C
TC
Feige
Jean-Jacques
JJ
Bailly
Sabine
S
D000818:Animals; D017209:Apoptosis; D001549:Benzamides / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D014355:Chagas Disease; D002522:Chlorocebus aethiops; D004149:Dioxoles / Q000494:pharmacology*; D004847:Epithelial Cells / Q000469:parasitology; D051379:Mice; D032383:Myocytes, Cardiac / Q000469:parasitology*; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000187:drug effects* / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity*; D014709:Vero Cells
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta