A PPARγ agonist enhances bacterial clearance through neutrophil extracellular trap formation and improves survival in sepsis

Detalhes bibliográficos
Autor(a) principal: Araújo, Cláudia V.
Data de Publicação: 2016
Outros Autores: 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.
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