Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NF kappa B binding sites

Autor(es)

Bonin, Camila P. ^[1] ; Baccarin, Raquel Y. A. ^[2] ; Nostell, Katarina ^[3] ; Nahum, Laila A. ^{[4, 5]} ; Fossum, Caroline ^[6] ; de Camargo, Maristela M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Vet Med, Dept Clin, BR-05508900 Sao Paulo - Brazil

^[3] Swedish Univ Agr Sci, Dept Clin Sci, S-75007 Uppsala - Sweden

^[4] Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, BR-30190002 Belo Horizonte, MG - Brazil

^[5] Fac Inforium Tecnol, BR-30130180 Belo Horizonte, MG - Brazil

^[6] Swedish Univ Agr Sci, Immunol Sect, Dept Biomed & Vet Publ Hlth, SE-75123 Uppsala - Sweden

• Tipo de documento: Artigo Científico
• Fonte: Biochemical and Biophysical Research Communications; v. 432, n. 2, p. 256-261, MAR 8 2013.
• Citações Web of Science: 7

Resumo

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 (NF kappa B) 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. (C) 2013 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 08/54811-1 - Regulacao da sinalizacao por lps em linfocitos b de equinos.
• Beneficiário: Maristela Martins de Camargo
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/04244-3 - Efeitos da desregulação da via UPR sobre a expressão da ciclina A1 em linfócitos B humanos.
• Beneficiário: Camila Bonin Pinto
• Modalidade de apoio: Bolsas no Brasil - Mestrado