Use este identificador para citar ou linkar para este item: https://www.arca.fiocruz.br/handle/icict/18679

Tipo de documento
Artigo
Direito Autoral
Acesso aberto
Coleções
Compartilhar

Estatísticas
Metadata
Mostrar registro completo

A PPARγ AGONIST ENHANCES BACTERIAL CLEARANCE THROUGH NEUTROPHIL EXTRACELLULAR TRAP FORMATION AND IMPROVES SURVIVAL IN SEPSIS
Araújo, Cláudia V. et al. | Data do documento: 2016
Autor(es)
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.
Afiliação
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.
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.
Resumo em Inglês
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.
Palavras-chave
Informação
Infecção
Sepse
PPAR
Armadilha extracelular de neutrófilos
Eliminação bacteriana
 
Palavras-chave em inglês
information
infection
sepsis
PPAR
neutrophil extracellular trap
bacterial elimination
 
Editor
Lippincott, Williams & Wilkins
Referência
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.
DOI
10.1097/SHK.0000000000000520
ISSN
1073-2322
Notas
Author manuscript; available in PMC 2017 April 01