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https://www.arca.fiocruz.br/handle/icict/33556
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ArtigoDireito Autoral
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Data de embargo
2050-01-01
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LIPOPOLYSACCHARIDE-INDUCED INHIBITION OF TRANSCRIPTION OF TLR4 IN VITRO IS REVERSED BY DEXAMETHASONE AND CORRELATES WITH PRESENCE OF CONSERVED NFκB BINDING SITES.
Autor(es)
Afiliação
Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Imunologia. São Paulo, SP, Brasil
Universidade de São Paulo. Faculdade de Medicina Veterinária. Departamento de Clínicas. São Paulo, SP, Brasil
Department of Clinical Sciences. Swedish University of Agricultural Sciences.Uppsala, Sweden
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/Faculdade Infórium de Tecnologia. Belo Horizonte, MG, Brazil
Department of Biomedicine and Veterinary Public Health. Section for Immunology. Swedish University of Agricultural Sciences. Uppsala, Sweden
Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Imunologia. São Paulo, SP, Brasil
Universidade de São Paulo. Faculdade de Medicina Veterinária. Departamento de Clínicas. São Paulo, SP, Brasil
Department of Clinical Sciences. Swedish University of Agricultural Sciences.Uppsala, Sweden
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/Faculdade Infórium de Tecnologia. Belo Horizonte, MG, Brazil
Department of Biomedicine and Veterinary Public Health. Section for Immunology. Swedish University of Agricultural Sciences. Uppsala, Sweden
Universidade de São Paulo. Instituto de Ciências Biomédicas. Departamento de Imunologia. São Paulo, SP, Brasil
Resumo em Inglês
Engagement of Toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) is a master trigger of the deleterious effects of septic shock. Horses and humans are considered the most sensitive species to septic shock, but the mechanisms explaining these phenomena remain elusive. Analysis of tlr4 promoters revealed high similarity among LPS-sensitive species (human, chimpanzee, and horse) and low similarity with LPS-resistant species (mouse and rat). Four conserved nuclear factor kappa B (NFκB) binding sites were found in the tlr4 promoter and two in the md2 promoter sequences that are likely to be targets for dexamethasone regulation. In vitro treatment of equine peripheral blood mononuclear cells (eqPBMC) with LPS decreased transcripts of tlr4 and increased transcription of md2 (myeloid differentiation factor 2) and cd14 (cluster of differentiation 14). Treatment with dexamethasone rescued transcription of tlr4 after LPS inhibition. LPS-induced transcription of md2 was inhibited in the presence of dexamethasone. Dexamethasone alone did not affect transcription of tlr4 and md2.
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