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Home / Equine Research Bank / Biochem Biophys Res Commun / Lipopolysaccharide-induced inhibition of transcription of tl...
Biochemical and biophysical research communications2013; 432(2); 256-261; doi: 10.1016/j.bbrc.2013.02.002

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.
Copyright © 2013 Elsevier Inc. All rights reserved.
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Publication Date: 2013-02-10 PubMed ID: 23402753PubMed Central: PMC3695733DOI: 10.1016/j.bbrc.2013.02.002Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research study investigates the effect of lipopolysaccharide (LPS) on the transcription of the Toll-like receptor 4 (TLR4) gene, how the drug dexamethasone reverses this effect, and the role of specific binding sites in this process. The study involved in vitro treatment of equine peripheral blood mononuclear cells and noted changes in transcription of TLR4 and other genes.

Background

  • The trigger for the detrimental effects of septic shock, a critical condition caused by infection, is the interaction between Toll-like receptor 4 (TLR4) and lipopolysaccharide (LPS).
  • While septic shock heavily affects horses and humans, the underlying mechanisms remain unclear.

Similarity in LPS-Sensitive Species

  • An analysis of TLR4 gene promoters, elements that control the transcription of the gene, revealed similarities among LPS-sensitive species (human, chimpanzee, and horse) and remarkable differences with LPS-resistant species like mouse and rat.

Dexamethasone and Conserved NFκB Binding Sites

  • Four conserved nuclear factor kappa B (NFκB) binding sites, regulatory sequences where NFκB protein can attach to DNA, were identified in the tlr4 gene promoters and two in the md2 gene promoter sequences. These sites are most probably the targets of dexamethasone regulation.

In Vitro Experiment Results

  • The researchers conducted an in vitro experiment with equine peripheral blood mononuclear cells. Upon LPS treatment, a decrease in tlr4 transcripts (mRNA molecules copied from the DNA of the tlr4 gene) and an increase in transcription of other genes such as md2 and cd14 were observed.
  • Dexamethasone treatment led to a rescuing or reversal of the tlr4 transcription levels after undergoing LPS-induced inhibition. Furthermore, LPS-induced transcription of the md2 gene was inhibited when dexamethasone was present.
  • Dexamethasone treatment alone did not seem to either increase or decrease the transcription levels of tlr4 and md2 genes.

Cite This Article

APA
Bonin CP, Baccarin RY, Nostell K, Nahum LA, Fossum C, de Camargo MM. (2013). Lipopolysaccharide-induced inhibition of transcription of tlr4 in vitro is reversed by dexamethasone and correlates with presence of conserved NFκB binding sites. Biochem Biophys Res Commun, 432(2), 256-261. https://doi.org/10.1016/j.bbrc.2013.02.002

Publication

Biochemical and biophysical research communications
ISSN: 1090-2104
NlmUniqueID: 0372516
Country: United States
Language: English
Volume: 432
Issue: 2
Pages: 256-261

Researcher Affiliations

Bonin, Camila P
  • Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900, Brazil. mila_bonin@yahoo.com.br
Baccarin, Raquel Y A
    Nostell, Katarina
      Nahum, Laila A
        Fossum, Caroline
          de Camargo, Maristela M

            MeSH Terms

            • Animals
            • Base Sequence
            • Binding Sites / drug effects
            • Cattle
            • Conserved Sequence
            • Dexamethasone / pharmacology
            • Horses
            • Humans
            • Lipopolysaccharide Receptors / genetics
            • Lipopolysaccharides / immunology
            • Lymphocyte Antigen 96 / genetics
            • Mice
            • NF-kappa B / metabolism
            • Pan troglodytes
            • Promoter Regions, Genetic
            • Rats
            • Swine
            • Toll-Like Receptor 4 / genetics
            • Transcription, Genetic / drug effects
            • Transcription, Genetic / immunology

            Grant Funding

            • D43 TW007012 / FIC NIH HHS
            • P50 AI098507 / NIAID NIH HHS
            • D43TW007012 / FIC NIH HHS

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