Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2015 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/13187 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil. |
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Ferrão, Patrícia MelloLevy, Claudia Masini d'AvilaAraujo-Jorge, Tania C.Degrave, Wim MauritsGonçalves, Antônio da SilvaGarzoni, Luciana RibeiroLima, Ana PaulaFeige, Jean JacquesBailly, SabineLima, Leila MendonçaWaghabi, Mariana Caldas2016-03-16T13:32:04Z2016-03-16T13:32:04Z2015FERRÃO, Patrícia Mello; et al. Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion. Plos One, v.10, n.5, e0124832, 15p, May 2015.1932-6203https://www.arca.fiocruz.br/handle/icict/1318710.1371/journal.pone.0124832engPublic Library of ScienceCruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biotecnologia e Fisiologia de Infecções Virais. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Programa Integrado de Doença de Chagas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho. Laboratório de Bioquímica e Biologia Molecular de Peptidases. Rio de Janeiro, RJ, Brasil.INSERM, Unité 1036, Grenoble, F-38054, France / Université Grenoble-Alpes—Grenoble, F-38041, France, CEA, DSV,iRTSV, Laboratory of Biology of Cancer and Infection, Grenoble, F-38054, France.INSERM, Unité 1036, Grenoble, F-38054, France / Université Grenoble-Alpes—Grenoble, F-38041, France, CEA, DSV,iRTSV, Laboratory of Biology of Cancer and Infection, Grenoble, F-38054, France.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Programa Integrado de Doença de Chagas. Rio de Janeiro, RJ, Brasil.Several studies indicate that the activity of cruzipain, the main lysosomal cysteine peptidase of Trypanosoma cruzi, contributes to parasite infectivity. In addition, the parasitic invasion process of mammalian host cells is described to be dependent on the activation of the host TGF-β signaling pathway by T. cruzi. Here, we tested the hypothesis that cruzipain could be an important activator of latent TGF-β and thereby trigger TGF-β-mediated events crucial for the development of Chagas disease. We found that live epimastigotes of T. cruzi, parasite lysates and purified cruzipain were able to activate latent TGF-β in vitro. This activation could be inhibited by the cysteine peptidase inhibitor Z-Phe-Ala-FMK. Moreover, transfected parasites overexpressing chagasin, a potent endogenous cruzipain inhibitor, prevented latent TGF-β activation. We also observed that T. cruzi invasion, as well as parasite intracellular growth, were inhibited by the administration of Z-Phe-Ala-FMK or anti-TGF-β neutralizing antibody to Vero cell cultures. We further demonstrated that addition of purified cruzipain enhanced the invasive activity of trypomastigotes and that this effect could be completely inhibited by addition of a neutralizing anti-TGF-β antibody. Taken together, these results demonstrate that the activities of cruzipain and TGF-β in the process of cell invasion are functionally linked. Our data suggest that cruzipain inhibition is an interesting chemotherapeutic approach for Chagas disease not only because of its trypanocidal activity, but also due to the inhibitory effect on TGF-β activation.Trypanosoma cruziChagas DiseaseTGF-βHost CellsCruzipainTrypanosoma cruziDoença de Chagasinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/13187/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALpatricia_ferrao_etal_IOC_2016.PDFpatricia_ferrao_etal_IOC_2016.PDFapplication/pdf5336252https://www.arca.fiocruz.br/bitstream/icict/13187/2/patricia_ferrao_etal_IOC_2016.PDF629a0b6f016cdc73060d004a72d20bd5MD52TEXTpatricia_ferrao_etal_IOC_2016.PDF.txtpatricia_ferrao_etal_IOC_2016.PDF.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion |
| title |
Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion |
| spellingShingle |
Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion Ferrão, Patrícia Mello Trypanosoma cruzi Chagas Disease TGF-β Host Cells Cruzipain Trypanosoma cruzi Doença de Chagas |
| title_short |
Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion |
| title_full |
Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion |
| title_fullStr |
Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion |
| title_full_unstemmed |
Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion |
| title_sort |
Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion |
| author |
Ferrão, Patrícia Mello |
| author_facet |
Ferrão, Patrícia Mello Levy, Claudia Masini d'Avila Araujo-Jorge, Tania C. Degrave, Wim Maurits Gonçalves, Antônio da Silva Garzoni, Luciana Ribeiro Lima, Ana Paula Feige, Jean Jacques Bailly, Sabine Lima, Leila Mendonça Waghabi, Mariana Caldas |
| author_role |
author |
| author2 |
Levy, Claudia Masini d'Avila Araujo-Jorge, Tania C. Degrave, Wim Maurits Gonçalves, Antônio da Silva Garzoni, Luciana Ribeiro Lima, Ana Paula Feige, Jean Jacques Bailly, Sabine Lima, Leila Mendonça Waghabi, Mariana Caldas |
| author2_role |
author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Ferrão, Patrícia Mello Levy, Claudia Masini d'Avila Araujo-Jorge, Tania C. Degrave, Wim Maurits Gonçalves, Antônio da Silva Garzoni, Luciana Ribeiro Lima, Ana Paula Feige, Jean Jacques Bailly, Sabine Lima, Leila Mendonça Waghabi, Mariana Caldas |
| dc.subject.en.pt_BR.fl_str_mv |
Trypanosoma cruzi Chagas Disease TGF-β Host Cells Cruzipain |
| topic |
Trypanosoma cruzi Chagas Disease TGF-β Host Cells Cruzipain Trypanosoma cruzi Doença de Chagas |
| dc.subject.decs.pt_BR.fl_str_mv |
Trypanosoma cruzi Doença de Chagas |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil. |
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2015 |
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2015 |
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2016-03-16T13:32:04Z |
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2016-03-16T13:32:04Z |
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FERRÃO, Patrícia Mello; et al. Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion. Plos One, v.10, n.5, e0124832, 15p, May 2015. |
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https://www.arca.fiocruz.br/handle/icict/13187 |
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1932-6203 |
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10.1371/journal.pone.0124832 |
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FERRÃO, Patrícia Mello; et al. Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion. Plos One, v.10, n.5, e0124832, 15p, May 2015. 1932-6203 10.1371/journal.pone.0124832 |
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