Gasdermin D inhibition prevents multiple organ dysfunction during sepsis by blocking NET formation

Página do item simplificado
dc.contributor.authorSilva, Camila Meirelles S.
dc.contributor.authorWanderley, Carlos Wagner S.
dc.contributor.authorVeras, Flavio P.
dc.contributor.authorSonego, Fabiane
dc.contributor.authorNascimento, Daniele C.
dc.contributor.authorGonçalves, Augusto V.
dc.contributor.authorMartins, Timna V.
dc.contributor.authorCólon, David F.
dc.contributor.authorBorges, Vanessa F.
dc.contributor.authorBrauer, Verônica S.
dc.contributor.authorDamasceno, Luis Eduardo A.
dc.contributor.authorSilva, Katiussia P. [UNESP]
dc.contributor.authorToller-Kawahisa, Juliana E.
dc.contributor.authorBatah, Sabrina S.
dc.contributor.authorSouza, Ana Letícia J.
dc.contributor.authorMonteiro, Valter S.
dc.contributor.authorOliveira, Antônio Edson R.
dc.contributor.authorDonate, Paula B.
dc.contributor.authorZoppi, Daniel
dc.contributor.authorBorges, Marcos C.
dc.contributor.authorAlmeida, Fausto
dc.contributor.authorNakaya, Helder I.
dc.contributor.authorFabro, Alexandre T.
dc.contributor.authorCunha, Thiago M.
dc.contributor.authorAlves-Filho, José Carlos
dc.contributor.authorZamboni, Dario S.
dc.contributor.authorCunha, Fernando Q.
dc.contributor.institutionCenter for Research in Inflammatory Diseases
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionPathology and Legal Medicine
dc.contributor.institutionSao Paulo
dc.date.accessioned2022-04-29T08:46:05Z
dc.date.available2022-04-29T08:46:05Z
dc.date.issued2021-12-23
dc.description.abstractMultiple organ dysfunction is the most severe outcome of sepsis progression and is highly correlated with a worse prognosis. Excessive neutrophil extracellular traps (NETs) are critical players in the development of organ failure during sepsis. Therefore, interventions targeting NET release would likely effectively prevent NET-based organ injury associated with this disease. Herein, we demonstrate that the pore-forming protein gasdermin D (GSDMD) is active in neutrophils from septic humans and mice and plays a crucial role in NET release. Inhibition of GSDMD with disulfiram or genic deletion abrogated NET formation, reducing multiple organ dysfunction and sepsis lethality. Mechanistically, we demonstrate that during sepsis, activation of the caspase-11/GSDMD pathway controls NET release by neutrophils during sepsis. In summary, our findings uncover a novel therapeutic use for disulfiram and suggest that GSDMD is a therapeutic target to improve sepsis treatment.en
dc.description.affiliationCenter for Research in Inflammatory Diseases
dc.description.affiliationDepartment of Biochemistry and Immunology
dc.description.affiliationDepartment of Pharmacology
dc.description.affiliationDepartment of Cellular and Molecular Biology and Pathogenic Bioagents Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto
dc.description.affiliationInstitute of Biosciences Sao Paulo State University, Botucatu
dc.description.affiliationPathology and Legal Medicine
dc.description.affiliationDepartment of Internal Medicine Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto
dc.description.affiliationHospital Israelita Albert Einstein Sao Paulo
dc.description.affiliationUnespInstitute of Biosciences Sao Paulo State University, Botucatu
dc.format.extent2702-2713
dc.identifierhttp://dx.doi.org/10.1182/blood.2021011525
dc.identifier.citationBlood, v. 138, n. 25, p. 2702-2713, 2021.
dc.identifier.doi10.1182/blood.2021011525
dc.identifier.issn1528-0020
dc.identifier.issn0006-4971
dc.identifier.scopus2-s2.0-85118989841
dc.identifier.urihttp://hdl.handle.net/11449/231550
dc.language.isoeng
dc.relation.ispartofBlood
dc.sourceScopus
dc.titleGasdermin D inhibition prevents multiple organ dysfunction during sepsis by blocking NET formationen
dc.typeArtigo
unesp.author.orcid0000-0001-8185-4435 0000-0001-8185-4435[1]
unesp.author.orcid0000-0003-2100-9963 0000-0003-2100-9963[2]
unesp.author.orcid0000-0002-6222-4064[3]
unesp.author.orcid0000-0002-0620-339X 0000-0002-0620-339X[5]
unesp.author.orcid0000-0002-1577-3677 0000-0002-1577-3677[6]
unesp.author.orcid0000-0002-6911-4765 0000-0002-6911-4765[8]
unesp.author.orcid0000-0003-2833-9244 0000-0003-2833-9244[11]
unesp.author.orcid0000-0002-9606-082X 0000-0002-9606-082X[12]
unesp.author.orcid0000-0002-9694-3489[14]
unesp.author.orcid0000-0003-3594-1209[15]
unesp.author.orcid0000-0003-1785-6713 0000-0003-1785-6713[16]
unesp.author.orcid0000-0001-8783-9009[17]
unesp.author.orcid0000-0001-8422-8894 0000-0001-8422-8894[18]
unesp.author.orcid0000-0002-3782-3698[21]
unesp.author.orcid0000-0001-5297-9108 0000-0001-5297-9108[22]
unesp.author.orcid0000-0002-7687-3161[23]
unesp.author.orcid0000-0003-1084-0065 0000-0003-1084-0065[24]
unesp.author.orcid0000-0002-9918-8714 0000-0002-9918-8714[25]
unesp.author.orcid0000-0002-7856-7512 0000-0002-7856-7512[26]
unesp.author.orcid0000-0003-4755-1670 0000-0003-4755-1670[27]

Arquivos

Coleções

Artigos - Clínica Médica - FMB