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SB-431542, A TRANSFORMING GROWTH FACTOR β INHIBITOR, IMPAIRS TRYPANOSOMA CRUZI INFECTION IN CARDIOMYOCYTES AND PARASITE CYCLE COMPLETION
Waghabi, Mariana C. et al. | Date Issued: 2007
Author
Waghabi, Mariana C.
Keramidas, Michelle
Calvet, Claudia M.
Meuser, Marcos
Soeiro, Maria de Nazaré C.
Lima, Leila Mendonça
Araujo-Jorge, Tania C.
Feige, Jean-Jacques
Bailly, Sabine
Affilliation
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Bioquímica e Biologia Molecular. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Institut National de la Santé et de la Recherche Médicale. Grenoble, France / Institut de Recherches en Technologies et Sciences pour le Vivant. France / Angiogenèse et Physiopathologie Vasculaire. Grenoble, France / Université Joseph Fourier, Grenoble, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Departamento de Bioquímica e Biologia Molecular. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Institut National de la Santé et de la Recherche Médicale. Grenoble, France / Institut de Recherches en Technologies et Sciences pour le Vivant. France / Angiogenèse et Physiopathologie Vasculaire. Grenoble, France / Université Joseph Fourier, Grenoble, France.
Institut National de la Santé et de la Recherche Médicale. Grenoble, France / Institut de Recherches en Technologies et Sciences pour le Vivant. France / Angiogenèse et Physiopathologie Vasculaire. Grenoble, France / Université Joseph Fourier, Grenoble, France.
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.
Keywords in Portuguese
SB-431542
Inibidor do fator de crescimento
Cardiomiócitos
Ciclo parasitário
Trypanosoma cruzi
Infecção
 
Keywords
SB-431542
Transforming growth factor inhibitor
Cardiomyocytes
Parasite Cycle
Trypanosoma cruzi Infection
 
Publisher
American Society for Microbiology
Citation
WAGHABI, Mariana C. et al. SB-431542, a transforming growth factor β inhibitor, impairs Trypanosoma cruzi infection in cardiomyocytes and parasite cycle completion. Antimicrobial Agents and Chemotherapy, v. 51, n. 8. p. 2905-2910, Aug. 2007.
DOI
10.1128/AAC.00022-07
ISSN
0066-4804