Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle

Detalhes bibliográficos
Autor(a) principal: Pons, Andrea Henriques
Data de Publicação: 2014
Outros Autores: Yu, Qing, Rayavarapu, Sree, Cohen, Tatiana V, Ampong, Beryl, Cha, Hee Jae, Jahnke, Vanessa, Van der Meulen, Jack, Wang, Daqing, Jiang, Weiwen, Kandimalla, Ekambar R, Agrawal, Sudhir, Spurney, Christopher F, Nagaraju, Kanneboyina
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/10615
Resumo: Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
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spelling Pons, Andrea HenriquesYu, QingRayavarapu, SreeCohen, Tatiana VAmpong, BerylCha, Hee JaeJahnke, VanessaVan der Meulen, JackWang, DaqingJiang, WeiwenKandimalla, Ekambar RAgrawal, SudhirSpurney, Christopher FNagaraju, Kanneboyina2015-06-01T19:34:24Z2015-06-01T19:34:24Z2014PONS, Andrea Henriques et al. Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle. Human Molecular Genetics, v.23, n.10, p. 2604-2607, 2014.1460-2083https://www.arca.fiocruz.br/handle/icict/1061510.1093/hmg/ddt656engOxford University PressRole of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleChildren’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.Children´s Hospital. Children’s National Medical Center.Center for Genetic Medicine Research. Division of Cardiology. Washington, DC,USAChildren’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA / The George Washington University. Department of Integrative Systems Biology. Washington, DC, USA.Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA.Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USAChildren’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USAChildren’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USAChildren’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USAIdera Pharmaceuticals, Inc.. Cambridge, MA, USA.Idera Pharmaceuticals, Inc., Cambridge, MA, USA.Idera Pharmaceuticals, Inc., Cambridge, MA, USA.Idera Pharmaceuticals, Inc., Cambridge, MA, USA.Children´s Hospital. Children’s National Medical Center.Center for Genetic Medicine Research. Division of Cardiology. Washington, DC,USAChildren´s Hospital. Children’s National Medical Center.Center for Genetic Medicine Research. Division of Cardiology. Washington, DC,USAAlthough the cause of Duchenne muscular dystrophy (DMD) is known, the specific factors that initiate and perpetuate disease progression are not well understood.We hypothesized that leaky dystrophin-deficient skeletal muscle releases endogenous danger signals (TLR ligands), which bind to Toll-like receptors (TLRs) on muscle andimmunecellsand activate downstreamprocesses that facilitate degeneration andregeneration in dystrophic skeletal muscle. Here, we demonstrate that dystrophin-deficient mousemuscle cells show increased expression of several cell-surface and endosomal TLRs. In vitro screening identified ssRNA as a relevant endogenous TLR7 ligand. TLR7 activation led to myd88-dependent production of pro-inflammatory cytokines in dystrophindeficient muscle cells, and cause significant degeneration/regeneration in vivo in mdx mouse muscle. Also, knockout of the central TLR adaptor protein, myd88 in mdx mice significantly improved skeletal and cardiac muscle function. Likewise, proof-of-concept experiments showed that treating young mdx mice with a TLR7/9 antagonist significantly reduced skeletal muscle inflammation and increased muscle force, suggesting that blocking this pathway may have therapeutic potential for DMD.Heart muscleDystrophin-deficient skeletalDuchenne muscular dystrophy (DMD)Toll-like receptors (TLRs)info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1914https://www.arca.fiocruz.br/bitstream/icict/10615/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALandrea_ponsetal_IOC_2014.pdfapplication/pdf1110246https://www.arca.fiocruz.br/bitstream/icict/10615/2/andrea_ponsetal_IOC_2014.pdfe55e29d1c818369b3de0a4fd8391aa81MD52TEXTandrea_ponsetal_IOC_2014.pdf.txtandrea_ponsetal_IOC_2014.pdf.txtExtracted texttext/plain61391https://www.arca.fiocruz.br/bitstream/icict/10615/3/andrea_ponsetal_IOC_2014.pdf.txtb35b80b8f7e9241cde17474fe47cf8afMD53icict/106152022-06-24 13:09:03.849oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-06-24T16:09:03Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle
title Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle
spellingShingle Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle
Pons, Andrea Henriques
Heart muscle
Dystrophin-deficient skeletal
Duchenne muscular dystrophy (DMD)
Toll-like receptors (TLRs)
title_short Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle
title_full Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle
title_fullStr Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle
title_full_unstemmed Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle
title_sort Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle
author Pons, Andrea Henriques
author_facet Pons, Andrea Henriques
Yu, Qing
Rayavarapu, Sree
Cohen, Tatiana V
Ampong, Beryl
Cha, Hee Jae
Jahnke, Vanessa
Van der Meulen, Jack
Wang, Daqing
Jiang, Weiwen
Kandimalla, Ekambar R
Agrawal, Sudhir
Spurney, Christopher F
Nagaraju, Kanneboyina
author_role author
author2 Yu, Qing
Rayavarapu, Sree
Cohen, Tatiana V
Ampong, Beryl
Cha, Hee Jae
Jahnke, Vanessa
Van der Meulen, Jack
Wang, Daqing
Jiang, Weiwen
Kandimalla, Ekambar R
Agrawal, Sudhir
Spurney, Christopher F
Nagaraju, Kanneboyina
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Pons, Andrea Henriques
Yu, Qing
Rayavarapu, Sree
Cohen, Tatiana V
Ampong, Beryl
Cha, Hee Jae
Jahnke, Vanessa
Van der Meulen, Jack
Wang, Daqing
Jiang, Weiwen
Kandimalla, Ekambar R
Agrawal, Sudhir
Spurney, Christopher F
Nagaraju, Kanneboyina
dc.subject.en.pt_BR.fl_str_mv Heart muscle
Dystrophin-deficient skeletal
Duchenne muscular dystrophy (DMD)
Toll-like receptors (TLRs)
topic Heart muscle
Dystrophin-deficient skeletal
Duchenne muscular dystrophy (DMD)
Toll-like receptors (TLRs)
description Children’s National Medical Center. Center for Genetic Medicine Research. Washington, DC,USA / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
publishDate 2014
dc.date.issued.fl_str_mv 2014
dc.date.accessioned.fl_str_mv 2015-06-01T19:34:24Z
dc.date.available.fl_str_mv 2015-06-01T19:34:24Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv PONS, Andrea Henriques et al. Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle. Human Molecular Genetics, v.23, n.10, p. 2604-2607, 2014.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/10615
dc.identifier.issn.pt_BR.fl_str_mv 1460-2083
dc.identifier.doi.pt_BR.fl_str_mv 10.1093/hmg/ddt656
identifier_str_mv PONS, Andrea Henriques et al. Role of toll-like receptors in the pathogenesis of dystrophin-deficient skeletal and heart muscle. Human Molecular Genetics, v.23, n.10, p. 2604-2607, 2014.
1460-2083
10.1093/hmg/ddt656
url https://www.arca.fiocruz.br/handle/icict/10615
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
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