SB-431542, a transforming growth factor beta inhibitor, impairs Trypanosoma cruzi infection in cardiomyocytes and parasite cycle completion. - Archive ouverte HAL Access content directly
Journal Articles Antimicrobial Agents and Chemotherapy Year : 2007

SB-431542, a transforming growth factor beta inhibitor, impairs Trypanosoma cruzi infection in cardiomyocytes and parasite cycle completion.

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Abstract

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.

Dates and versions

inserm-00376225 , version 1 (17-04-2009)

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Waghabi C. Mariana, Michelle Keramidas, Claudia M. Calvet, Marcos Meuser, Maria de Nazaré C Soeiro, et al.. SB-431542, a transforming growth factor beta inhibitor, impairs Trypanosoma cruzi infection in cardiomyocytes and parasite cycle completion.. Antimicrobial Agents and Chemotherapy, 2007, 51 (8), pp.2905-10. ⟨10.1128/AAC.00022-07⟩. ⟨inserm-00376225⟩
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