Macrophage-derived MicroRNA-21 drives overwhelming glycolytic and inflammatory response during sepsis via repression of the PGE2/IL-10 axis

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Autor(es): dc.contributorVanderbilt University Medical Center-
Autor(es): dc.contributorIndiana Biosciences Research Institute-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.creatorDe Melo, Paulo-
Autor(es): dc.creatorAlvarez, Annie Rocio Pineros-
Autor(es): dc.creatorYe, Xiang-
Autor(es): dc.creatorBlackman, Amondrea-
Autor(es): dc.creatorAlves-Filho, Jose Carlos-
Autor(es): dc.creatorMedeiros, Alexandra I.-
Autor(es): dc.creatorRathmell, Jeffrey-
Autor(es): dc.creatorPua, Heather-
Autor(es): dc.creatorSerezani, C. Henrique-
Data de aceite: dc.date.accessioned2025-08-21T21:08:05Z-
Data de disponibilização: dc.date.available2025-08-21T21:08:05Z-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2022-04-29-
Data de envio: dc.date.issued2021-08-01-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.4049/jimmunol.2001251-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/229255-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/229255-
Descrição: dc.descriptionMyeloid cells are critical for systemic inflammation, microbial control, and organ damage during sepsis. MicroRNAs are small noncoding RNAs that can dictate the outcome of sepsis. The role of myeloid-based expression of microRNA-21 (miR-21) in sepsis is inconclusive. In this study, we show that sepsis enhanced miR-21 expression in both peritoneal macrophages and neutrophils from septic C57BL/6J mice, and the deletion of miR-21 locus in myeloid cells (miR-21Δmyel mice) enhanced animal survival, decreased bacterial growth, decreased systemic inflammation, and decreased organ damage. Resistance to sepsis was associated with a reduction of aerobic glycolysis and increased levels of the anti-inflammatory mediators PGE2 and IL-10 in miR-21Dmyel in vivo and in vitro. Using blocking Abs and pharmacological tools, we discovered that increased survival and decreased systemic inflammation in septic miR-21Δmyel mice is dependent on PGE2/IL-10-mediated inhibition of glycolysis. Together, these findings demonstrate that expression of miR-21 in myeloid cells orchestrates the balance between anti-inflammatory mediators and metabolic reprogramming that drives cytokine storm during sepsis.-
Descrição: dc.descriptionNational Heart, Lung, and Blood Institute-
Descrição: dc.descriptionNational Institute of Allergy and Infectious Diseases-
Descrição: dc.descriptionNational Institute of Diabetes and Digestive and Kidney Diseases-
Descrição: dc.descriptionNational Institutes of Health-
Descrição: dc.descriptionDiabetes Research and Training Center-
Descrição: dc.descriptionDivision of Infectious Diseases Department of Medicine Vanderbilt University Medical Center-
Descrição: dc.descriptionIndiana Biosciences Research Institute-
Descrição: dc.descriptionDepartment of Pathology Microbiology and Immunology Vanderbilt University Medical Center-
Descrição: dc.descriptionDepartment of Pharmacology School of Medicine of Ribeirão Preto University of São Paulo-
Descrição: dc.descriptionDepartment of Biological Sciences School of Pharmaceutical Sciences São Paulo State University, Araraquara-
Descrição: dc.descriptionDepartment of Biochemistry and Immunology Faculty of Medicine of Ribeirão Preto University of São Paulo, Ribeirão Preto-
Descrição: dc.descriptionVanderbilt Center for Immunobiology Vanderbilt University Medical Center-
Descrição: dc.descriptionVanderbilt Institute for Infection Inflammation and Immunity Vanderbilt University Medical Center-
Descrição: dc.descriptionDepartment of Biological Sciences School of Pharmaceutical Sciences São Paulo State University, Araraquara-
Descrição: dc.descriptionNational Institutes of Health: 1S10OD018015-
Descrição: dc.descriptionNational Institutes of Health: 5R01DK105550-08-
Descrição: dc.descriptionDiabetes Research and Training Center: DK-20593-
Descrição: dc.descriptionNational Institutes of Health: DK12214701A1-
Descrição: dc.descriptionNational Institutes of Health: K08AI116949-
Descrição: dc.descriptionNational Institutes of Health: R01HL124159-
Formato: dc.format902-912-
Idioma: dc.languageen-
Relação: dc.relationJournal of Immunology-
???dc.source???: dc.sourceScopus-
Título: dc.titleMacrophage-derived MicroRNA-21 drives overwhelming glycolytic and inflammatory response during sepsis via repression of the PGE2/IL-10 axis-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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