Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophages
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| 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/53217 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Morfologia e Morfogênese Viral. Rio de Janeiro, Rio de Janeiro, Brasil. |
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Teixeira, Gabrielly SbanoAndrade, Audrien AlvesTorres, Lauana RibasLima, Dinair CoutoMoreira, Otacilio C.Abreu, Rayane da SilvaWaghabi, Mariana CaldasSouza, Elen Mello de2022-06-13T11:23:16Z2022-06-13T11:23:16Z2022TEIXEIRA, Gabrielly Sbano et al. Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophages. Journal of Medical Virology, p. 1 - 10, May 2022.1096-9071https://www.arca.fiocruz.br/handle/icict/5321710.1002/jmv.27879engWileyVírus da DengueMacrófagosSinalização clássica de TGF-β1Inibidor do receptor de TGFβClassical TGF‐β1 signalingDengue virusGW788388MacrophagesTGFβ receptor inhibitorTGF‐β1Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophagesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Morfologia e Morfogênese Viral. Rio de Janeiro, Rio de Janeiro, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Mosquitos Transmissores de Hematozoários. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Plataforma de PCR em Tempo Real RPT09A, Laboratório de Biologia Molecular e Doenças Endêmicas, 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 Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Morfologia e Morfogênese Viral. Rio de Janeiro, Rio de Janeiro, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Virologia Molecular. Rio de Janeiro, RJ, Brasil.Dengue fever, caused by the dengue virus (DENV‐1, −2, −3, and −4), affects millions of people in the tropical and subtropical regions worldwide. Severe dengue is correlated with high viraemia and cytokine storm, such as high levels of transforming growth factor‐β1 (TGF‐β1) in the patient's serum. Here, the TGF‐β1 signaling was investigated in the context of in vitro viral clearance. Macrophages were infected with DENV‐2 at MOI 5 and treated with the TGF‐β receptor 1 and 2 inhibitor, GW788388. TGF‐β1 expression, signal transduction and viral load were evaluated 48 h after DENV‐2 infection by enzyme‐linked immunoassay, immunofluorescence, and RT‐qPCR assays. Total TGF‐β1 levelwas reduced in 15%afterDENV‐2 infection, but the secretion of its biologically active form increased threefold during infection, which was followed by the phosphorylation of Smad2 protein. Phosphorylation of Smad2 was reduced by treatment with GW788388 and it was correlated with reduced cytokine production. Importantly, treatment led to a dose‐dependent reduction in viral load, ranging from 6.6×105 RNA copies/ml in untreated cultures to 2.3 × 103 RNA copies/ml in cultures treated with 2 ng/ml of GW788388. The anti‐TGF‐β1 antibody treatment also induced a significant reduction in viral load to 1.6 × 103 RNA copies/ml. On the other hand, the addition of recombinant TGF‐β1 in infected cultures promoted an increase in viral load to 7.0 × 106 RNA copies/ml. These results support that TGF‐β1 plays a significant role in DENV‐2 replication into macrophages and suggest that targeting TGF‐β1 may represent an alternative therapeutic strategy to be explored in dengue infection.info: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/53217/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALGabriellyTeixeira_LuanaTorres_etal_IOC_2022.pdfGabriellyTeixeira_LuanaTorres_etal_IOC_2022.pdfapplication/pdf1892916https://www.arca.fiocruz.br/bitstream/icict/53217/2/GabriellyTeixeira_LuanaTorres_etal_IOC_2022.pdf83651964c0d92d65c5c4e05151d7a274MD52icict/532172023-09-14 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| dc.title.pt_BR.fl_str_mv |
Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophages |
| title |
Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophages |
| spellingShingle |
Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophages Teixeira, Gabrielly Sbano Vírus da Dengue Macrófagos Sinalização clássica de TGF-β1 Inibidor do receptor de TGFβ Classical TGF‐β1 signaling Dengue virus GW788388 Macrophages TGFβ receptor inhibitor TGF‐β1 |
| title_short |
Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophages |
| title_full |
Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophages |
| title_fullStr |
Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophages |
| title_full_unstemmed |
Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophages |
| title_sort |
Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophages |
| author |
Teixeira, Gabrielly Sbano |
| author_facet |
Teixeira, Gabrielly Sbano Andrade, Audrien Alves Torres, Lauana Ribas Lima, Dinair Couto Moreira, Otacilio C. Abreu, Rayane da Silva Waghabi, Mariana Caldas Souza, Elen Mello de |
| author_role |
author |
| author2 |
Andrade, Audrien Alves Torres, Lauana Ribas Lima, Dinair Couto Moreira, Otacilio C. Abreu, Rayane da Silva Waghabi, Mariana Caldas Souza, Elen Mello de |
| author2_role |
author author author author author author author |
| dc.contributor.author.fl_str_mv |
Teixeira, Gabrielly Sbano Andrade, Audrien Alves Torres, Lauana Ribas Lima, Dinair Couto Moreira, Otacilio C. Abreu, Rayane da Silva Waghabi, Mariana Caldas Souza, Elen Mello de |
| dc.subject.other.pt_BR.fl_str_mv |
Vírus da Dengue Macrófagos Sinalização clássica de TGF-β1 Inibidor do receptor de TGFβ |
| topic |
Vírus da Dengue Macrófagos Sinalização clássica de TGF-β1 Inibidor do receptor de TGFβ Classical TGF‐β1 signaling Dengue virus GW788388 Macrophages TGFβ receptor inhibitor TGF‐β1 |
| dc.subject.en.pt_BR.fl_str_mv |
Classical TGF‐β1 signaling Dengue virus GW788388 Macrophages TGFβ receptor inhibitor TGF‐β1 |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Morfologia e Morfogênese Viral. Rio de Janeiro, Rio de Janeiro, Brasil. |
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2022 |
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2022-06-13T11:23:16Z |
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2022-06-13T11:23:16Z |
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2022 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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TEIXEIRA, Gabrielly Sbano et al. Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophages. Journal of Medical Virology, p. 1 - 10, May 2022. |
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https://www.arca.fiocruz.br/handle/icict/53217 |
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1096-9071 |
| dc.identifier.doi.none.fl_str_mv |
10.1002/jmv.27879 |
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TEIXEIRA, Gabrielly Sbano et al. Suppression of TGF‐β/Smad2 signaling by GW788388 enhances DENV‐2 clearance in macrophages. Journal of Medical Virology, p. 1 - 10, May 2022. 1096-9071 10.1002/jmv.27879 |
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