title: Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites.
abstract: 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.
authors: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900, Brazil. mila_bonin@yahoo.com.br
authors: Camila P
authors: CP
authors: Bonin
authors: Raquel Y A
authors: RY
authors: Baccarin
authors: Katarina
authors: K
authors: Nostell
authors: Laila A
authors: LA
authors: Nahum
authors: Caroline
authors: C
authors: Fossum
authors: Maristela M
authors: MM
authors: de Camargo
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000187:drug effects; D002417:Cattle; D017124:Conserved Sequence; D003907:Dexamethasone / Q000494:pharmacology*; D006736:Horses; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology*; D051218:Lymphocyte Antigen 96 / Q000235:genetics; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D002679:Pan troglodytes; D011401:Promoter Regions, Genetic; D051381:Rats; D013552:Swine; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects* / Q000276:immunology*
chemical_list: D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D003907:Dexamethasone
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