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lüll SB-431542, a transforming growth factor beta inhibitor, impairs Trypanosoma cruzi infection in cardiomyocytes and parasite cycle completion Waghabi MC; Keramidas M; Calvet CM; Meuser M; de Nazare C Soeiro M; Mendonca-Lima L; Araujo-Jorge TC; Feige JJ; Bailly SAntimicrob Agents Chemother 2007[Aug]; 51 (8): 2905-10The 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.|Animals[MESH]|Apoptosis[MESH]|Benzamides/*pharmacology[MESH]|Cell Cycle/drug effects[MESH]|Cells, Cultured[MESH]|Chagas Disease[MESH]|Chlorocebus aethiops[MESH]|Dioxoles/*pharmacology[MESH]|Epithelial Cells/parasitology[MESH]|Mice[MESH]|Myocytes, Cardiac/*parasitology[MESH]|Receptors, Transforming Growth Factor beta/*antagonists & inhibitors[MESH]|Signal Transduction/drug effects[MESH]|Transforming Growth Factor beta/*drug effects/metabolism[MESH]|Trypanosoma cruzi/cytology/drug effects/growth & development/*pathogenicity[MESH]|Vero Cells[MESH] |