A PPARγ agonist enhances bacterial clearance through neutrophil extracellular trap formation and improves survival in sepsis
Autor(a) principal: | |
---|---|
Data de Publicação: | 2016 |
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/18679 |
Resumo: | Author manuscript; available in PMC 2017 April 01 |
id |
CRUZ_99fe272089a8a25e601f8f3463136290 |
---|---|
oai_identifier_str |
oai:www.arca.fiocruz.br:icict/18679 |
network_acronym_str |
CRUZ |
network_name_str |
Repositório Institucional da FIOCRUZ (ARCA) |
repository_id_str |
2135 |
spelling |
Araújo, Cláudia V.Campbell, ClarissaAlbuquerque, Cassiano F. Gonçalves deMolinaro, RaphaelCody, Mark J.Yost, Christian C.Bozza, Patrícia T.Zimmerman, Guy A.Weyrich, Andrew S.Faria Neto, Hugo C. CastroSilva, Adriana R.2017-04-27T12:39:13Z2017-04-27T12:39:13Z2016ARAÚJO, Cláudia V. et al. A PPARγ agonist enhances bacterial clearance through neutrophil extracellular trap formation and improves survival in sepsis. Shock, v.45, n.4, p.393-403, Apr. 2016.1073-2322https://www.arca.fiocruz.br/handle/icict/1867910.1097/SHK.00000000000005201540-0514Author manuscript; available in PMC 2017 April 01Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil / University of Utah School of Medicine. Department of Internal Medicine. Salt Lake City, Utah, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.University of Utah School of Medicine. Department of Pediatrics. Eccles Institute of Human Genetics. Salt Lake City, Utah, USA / University of Utah School of Medicine. Program in Molecular Medicine. Eccles Institute of Human Genetics. Salt Lake City, Utah, USA.University of Utah School of Medicine. Department of Pediatrics. Eccles Institute of Human Genetics. Salt Lake City, Utah, USA / University of Utah School of Medicine. Program in Molecular Medicine. Eccles Institute of Human Genetics. Salt Lake City, Utah, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.University of Utah School of Medicine. Department of Internal Medicine. Salt Lake City, Utah, USA / University of Utah School of Medicine. Program in Molecular Medicine. Eccles Institute of Human Genetics. Salt Lake City, Utah, USA.University of Utah School of Medicine. Department of Internal Medicine. Salt Lake City, Utah, USA / University of Utah School of Medicine. Program in Molecular Medicine. Eccles Institute of Human Genetics. Salt Lake City, Utah, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ. Brasil.Dysregulation of the inflammatory response against infection contributes to mortality in sepsis. Inflammation provides critical host defense, but it can cause tissue damage, multiple organ failure, and death. Because the nuclear transcription factor peroxisome proliferator-activated receptor γ (PPARγ) exhibits therapeutic potential, we characterized the role of PPARγ in sepsis. We analyzed severity of clinical signs, survival rates, cytokine production, leukocyte influx, and bacterial clearance in a cecal ligation and puncture (CLP) model of sepsis in Swiss mice. The PPARγ agonist rosiglitazone treatment improved clinical status and mortality, while increasing IL-10 production and decreasing TNF-α and IL-6 levels, and peritoneal neutrophil accumulation 24 h after CLP. We noted increased bacterial killing in rosiglitazone treated mice, correlated with increased generation of reactive oxygen species. Polymorphonuclear leukocytes (PMN) incubated with LPS or Escherichia coli and rosiglitazone increased peritoneal neutrophil extracellular trap (NET)-mediated bacterial killing, an effect reversed by the PPARγ antagonist (GW 9662) treatment. Rosiglitazone also enhanced the release of histones by PMN, a surrogate marker of NET formation, effect abolished by GW 9662. Rosiglitazone modulated the inflammatory response and increased bacterial clearance through PPARγ activation and NET formation, combining immunomodulatory and host-dependent anti-bacterial effects and, therefore, warrants further study as a potential therapeutic agent in sepsis.engLippincott, Williams & WilkinsInformaçãoInfecçãoSepsePPARArmadilha extracelular de neutrófilosEliminação bacterianainformationinfectionsepsisPPARneutrophil extracellular trapbacterial eliminationA PPARγ agonist enhances bacterial clearance through neutrophil extracellular trap formation and improves survival in sepsisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo: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/18679/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALclaudia_varaujo_etla_IOC_2016.pdfclaudia_varaujo_etla_IOC_2016.pdfapplication/pdf4273024https://www.arca.fiocruz.br/bitstream/icict/18679/2/claudia_varaujo_etla_IOC_2016.pdf31d929dce3ff5bfcbb4a267a51cb7331MD52TEXTclaudia_varaujo_etla_IOC_2016.pdf.txtclaudia_varaujo_etla_IOC_2016.pdf.txtExtracted texttext/plain59175https://www.arca.fiocruz.br/bitstream/icict/18679/3/claudia_varaujo_etla_IOC_2016.pdf.txta36558d541b7318ccf5f3b560dc68713MD53icict/186792023-09-14 15:53:43.434oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-14T18:53:43Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
dc.title.pt_BR.fl_str_mv |
A PPARγ agonist enhances bacterial clearance through neutrophil extracellular trap formation and improves survival in sepsis |
title |
A PPARγ agonist enhances bacterial clearance through neutrophil extracellular trap formation and improves survival in sepsis |
spellingShingle |
A PPARγ agonist enhances bacterial clearance through neutrophil extracellular trap formation and improves survival in sepsis Araújo, Cláudia V. Informação Infecção Sepse PPAR Armadilha extracelular de neutrófilos Eliminação bacteriana information infection sepsis PPAR neutrophil extracellular trap bacterial elimination |
title_short |
A PPARγ agonist enhances bacterial clearance through neutrophil extracellular trap formation and improves survival in sepsis |
title_full |
A PPARγ agonist enhances bacterial clearance through neutrophil extracellular trap formation and improves survival in sepsis |
title_fullStr |
A PPARγ agonist enhances bacterial clearance through neutrophil extracellular trap formation and improves survival in sepsis |
title_full_unstemmed |
A PPARγ agonist enhances bacterial clearance through neutrophil extracellular trap formation and improves survival in sepsis |
title_sort |
A PPARγ agonist enhances bacterial clearance through neutrophil extracellular trap formation and improves survival in sepsis |
author |
Araújo, Cláudia V. |
author_facet |
Araújo, Cláudia V. Campbell, Clarissa Albuquerque, Cassiano F. Gonçalves de Molinaro, Raphael Cody, Mark J. Yost, Christian C. Bozza, Patrícia T. Zimmerman, Guy A. Weyrich, Andrew S. Faria Neto, Hugo C. Castro Silva, Adriana R. |
author_role |
author |
author2 |
Campbell, Clarissa Albuquerque, Cassiano F. Gonçalves de Molinaro, Raphael Cody, Mark J. Yost, Christian C. Bozza, Patrícia T. Zimmerman, Guy A. Weyrich, Andrew S. Faria Neto, Hugo C. Castro Silva, Adriana R. |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Araújo, Cláudia V. Campbell, Clarissa Albuquerque, Cassiano F. Gonçalves de Molinaro, Raphael Cody, Mark J. Yost, Christian C. Bozza, Patrícia T. Zimmerman, Guy A. Weyrich, Andrew S. Faria Neto, Hugo C. Castro Silva, Adriana R. |
dc.subject.other.pt_BR.fl_str_mv |
Informação Infecção Sepse PPAR Armadilha extracelular de neutrófilos Eliminação bacteriana |
topic |
Informação Infecção Sepse PPAR Armadilha extracelular de neutrófilos Eliminação bacteriana information infection sepsis PPAR neutrophil extracellular trap bacterial elimination |
dc.subject.en.pt_BR.fl_str_mv |
information infection sepsis PPAR neutrophil extracellular trap bacterial elimination |
description |
Author manuscript; available in PMC 2017 April 01 |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016 |
dc.date.accessioned.fl_str_mv |
2017-04-27T12:39:13Z |
dc.date.available.fl_str_mv |
2017-04-27T12:39:13Z |
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 |
ARAÚJO, Cláudia V. et al. A PPARγ agonist enhances bacterial clearance through neutrophil extracellular trap formation and improves survival in sepsis. Shock, v.45, n.4, p.393-403, Apr. 2016. |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/18679 |
dc.identifier.issn.pt_BR.fl_str_mv |
1073-2322 |
dc.identifier.doi.none.fl_str_mv |
10.1097/SHK.0000000000000520 |
dc.identifier.eissn.none.fl_str_mv |
1540-0514 |
identifier_str_mv |
ARAÚJO, Cláudia V. et al. A PPARγ agonist enhances bacterial clearance through neutrophil extracellular trap formation and improves survival in sepsis. Shock, v.45, n.4, p.393-403, Apr. 2016. 1073-2322 10.1097/SHK.0000000000000520 1540-0514 |
url |
https://www.arca.fiocruz.br/handle/icict/18679 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Lippincott, Williams & Wilkins |
publisher.none.fl_str_mv |
Lippincott, Williams & Wilkins |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
instname_str |
Fundação Oswaldo Cruz (FIOCRUZ) |
instacron_str |
FIOCRUZ |
institution |
FIOCRUZ |
reponame_str |
Repositório Institucional da FIOCRUZ (ARCA) |
collection |
Repositório Institucional da FIOCRUZ (ARCA) |
bitstream.url.fl_str_mv |
https://www.arca.fiocruz.br/bitstream/icict/18679/1/license.txt https://www.arca.fiocruz.br/bitstream/icict/18679/2/claudia_varaujo_etla_IOC_2016.pdf https://www.arca.fiocruz.br/bitstream/icict/18679/3/claudia_varaujo_etla_IOC_2016.pdf.txt |
bitstream.checksum.fl_str_mv |
5a560609d32a3863062d77ff32785d58 31d929dce3ff5bfcbb4a267a51cb7331 a36558d541b7318ccf5f3b560dc68713 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ) |
repository.mail.fl_str_mv |
repositorio.arca@fiocruz.br |
_version_ |
1813009301830107136 |