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

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorCenter for Research in Inflammatory Diseases-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorPathology and Legal Medicine-
Autor(es): dc.contributorSao Paulo-
Autor(es): dc.creatorSilva, Camila Meirelles S.-
Autor(es): dc.creatorWanderley, Carlos Wagner S.-
Autor(es): dc.creatorVeras, Flavio P.-
Autor(es): dc.creatorSonego, Fabiane-
Autor(es): dc.creatorNascimento, Daniele C.-
Autor(es): dc.creatorGonçalves, Augusto V.-
Autor(es): dc.creatorMartins, Timna V.-
Autor(es): dc.creatorCólon, David F.-
Autor(es): dc.creatorBorges, Vanessa F.-
Autor(es): dc.creatorBrauer, Verônica S.-
Autor(es): dc.creatorDamasceno, Luis Eduardo A.-
Autor(es): dc.creatorSilva, Katiussia P.-
Autor(es): dc.creatorToller-Kawahisa, Juliana E.-
Autor(es): dc.creatorBatah, Sabrina S.-
Autor(es): dc.creatorSouza, Ana Letícia J.-
Autor(es): dc.creatorMonteiro, Valter S.-
Autor(es): dc.creatorOliveira, Antônio Edson R.-
Autor(es): dc.creatorDonate, Paula B.-
Autor(es): dc.creatorZoppi, Daniel-
Autor(es): dc.creatorBorges, Marcos C.-
Autor(es): dc.creatorAlmeida, Fausto-
Autor(es): dc.creatorNakaya, Helder I.-
Autor(es): dc.creatorFabro, Alexandre T.-
Autor(es): dc.creatorCunha, Thiago M.-
Autor(es): dc.creatorAlves-Filho, José Carlos-
Autor(es): dc.creatorZamboni, Dario S.-
Autor(es): dc.creatorCunha, Fernando Q.-
Data de aceite: dc.date.accessioned2025-08-21T15:54:23Z-
Data de disponibilização: dc.date.available2025-08-21T15:54:23Z-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2021-12-22-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1182/blood.2021011525-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/231550-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/231550-
Descrição: dc.descriptionMultiple 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.-
Descrição: dc.descriptionCenter for Research in Inflammatory Diseases-
Descrição: dc.descriptionDepartment of Biochemistry and Immunology-
Descrição: dc.descriptionDepartment of Pharmacology-
Descrição: dc.descriptionDepartment of Cellular and Molecular Biology and Pathogenic Bioagents Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto-
Descrição: dc.descriptionInstitute of Biosciences Sao Paulo State University, Botucatu-
Descrição: dc.descriptionPathology and Legal Medicine-
Descrição: dc.descriptionDepartment of Internal Medicine Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto-
Descrição: dc.descriptionHospital Israelita Albert Einstein Sao Paulo-
Descrição: dc.descriptionInstitute of Biosciences Sao Paulo State University, Botucatu-
Formato: dc.format2702-2713-
Idioma: dc.languageen-
Relação: dc.relationBlood-
???dc.source???: dc.sourceScopus-
Título: dc.titleGasdermin D inhibition prevents multiple organ dysfunction during sepsis by blocking NET formation-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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