Propofol suppresses tumor necrosis factor-α biosynthesis in lipopolysaccharide-stimulated macrophages possibly through downregulation of nuclear factor-kappa B-mediated toll-like receptor 4 gene expression

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Abstract

Lipopolysaccharide (LPS), a gram-negative bacterial outer membrane component, can activate macrophages via a toll-like receptor 4-dependent pathway. Our previous study has shown that propofol, an intravenous anesthetic reagent, has anti-inflammatory effects. This study was further aimed to evaluate the roles of toll-like receptor 4 in propofol-caused suppression of tumor necrosis factor-α (TNF-α) biosynthesis in LPS-stimulated macrophages and its possible molecular mechanisms. Exposure of macrophages to propofol and LPS did not affect cell viability. Meanwhile, the LPS-caused augmentations in the productions of TNF-α protein and mRNA were significantly decreased following incubation with a therapeutic concentration of propofol (50 μM). Analysis of toll-like receptor 4 small interference (si)RNA revealed that this membrane receptor might participate in the propofol-caused suppression of TNF-α biosynthesis. Treatment of macrophages with LPS-induced toll-like receptor 4 protein and mRNA productions. Propofol at a clinically relevant concentration could inhibit such induction. In parallel, the LPS-induced translocation and transactivation of transcription factor nuclear factor-kappa B (NFκB) were significantly alleviated following propofol incubation. There are several NFκB DNA-binding motifs found in the promoter region of toll-like receptor 4. Therefore, this study shows that propofol at a therapeutic concentration can downregulate TNF-α biosynthesis possibly via inhibition of NFκB-mediated toll-like receptor 4 gene expression.

Original languageEnglish
Pages (from-to)465-471
Number of pages7
JournalChemico-Biological Interactions
Volume180
Issue number3
DOIs
Publication statusPublished - Aug 14 2009

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Toll-Like Receptor 4
NF-kappa B
Macrophages
Biosynthesis
Propofol
Gene expression
Lipopolysaccharides
Down-Regulation
Tumor Necrosis Factor-alpha
Gene Expression
Intravenous Anesthetics
Membranes
Messenger RNA
Nucleotide Motifs
RNA Interference
Genetic Promoter Regions
Transcriptional Activation
Cell Survival
Proteins
Anti-Inflammatory Agents

Keywords

  • LPS
  • Macrophages
  • NFκB
  • Propofol
  • TNF-α
  • Toll-like receptor 4

ASJC Scopus subject areas

  • Toxicology

Cite this

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title = "Propofol suppresses tumor necrosis factor-α biosynthesis in lipopolysaccharide-stimulated macrophages possibly through downregulation of nuclear factor-kappa B-mediated toll-like receptor 4 gene expression",
abstract = "Lipopolysaccharide (LPS), a gram-negative bacterial outer membrane component, can activate macrophages via a toll-like receptor 4-dependent pathway. Our previous study has shown that propofol, an intravenous anesthetic reagent, has anti-inflammatory effects. This study was further aimed to evaluate the roles of toll-like receptor 4 in propofol-caused suppression of tumor necrosis factor-α (TNF-α) biosynthesis in LPS-stimulated macrophages and its possible molecular mechanisms. Exposure of macrophages to propofol and LPS did not affect cell viability. Meanwhile, the LPS-caused augmentations in the productions of TNF-α protein and mRNA were significantly decreased following incubation with a therapeutic concentration of propofol (50 μM). Analysis of toll-like receptor 4 small interference (si)RNA revealed that this membrane receptor might participate in the propofol-caused suppression of TNF-α biosynthesis. Treatment of macrophages with LPS-induced toll-like receptor 4 protein and mRNA productions. Propofol at a clinically relevant concentration could inhibit such induction. In parallel, the LPS-induced translocation and transactivation of transcription factor nuclear factor-kappa B (NFκB) were significantly alleviated following propofol incubation. There are several NFκB DNA-binding motifs found in the promoter region of toll-like receptor 4. Therefore, this study shows that propofol at a therapeutic concentration can downregulate TNF-α biosynthesis possibly via inhibition of NFκB-mediated toll-like receptor 4 gene expression.",
keywords = "LPS, Macrophages, NFκB, Propofol, TNF-α, Toll-like receptor 4",
author = "Gong-Jhe Wu and Ta-Liang Chen and Chang, {Chia Chen} and Ruei-Ming Chen",
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T1 - Propofol suppresses tumor necrosis factor-α biosynthesis in lipopolysaccharide-stimulated macrophages possibly through downregulation of nuclear factor-kappa B-mediated toll-like receptor 4 gene expression

AU - Wu, Gong-Jhe

AU - Chen, Ta-Liang

AU - Chang, Chia Chen

AU - Chen, Ruei-Ming

PY - 2009/8/14

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N2 - Lipopolysaccharide (LPS), a gram-negative bacterial outer membrane component, can activate macrophages via a toll-like receptor 4-dependent pathway. Our previous study has shown that propofol, an intravenous anesthetic reagent, has anti-inflammatory effects. This study was further aimed to evaluate the roles of toll-like receptor 4 in propofol-caused suppression of tumor necrosis factor-α (TNF-α) biosynthesis in LPS-stimulated macrophages and its possible molecular mechanisms. Exposure of macrophages to propofol and LPS did not affect cell viability. Meanwhile, the LPS-caused augmentations in the productions of TNF-α protein and mRNA were significantly decreased following incubation with a therapeutic concentration of propofol (50 μM). Analysis of toll-like receptor 4 small interference (si)RNA revealed that this membrane receptor might participate in the propofol-caused suppression of TNF-α biosynthesis. Treatment of macrophages with LPS-induced toll-like receptor 4 protein and mRNA productions. Propofol at a clinically relevant concentration could inhibit such induction. In parallel, the LPS-induced translocation and transactivation of transcription factor nuclear factor-kappa B (NFκB) were significantly alleviated following propofol incubation. There are several NFκB DNA-binding motifs found in the promoter region of toll-like receptor 4. Therefore, this study shows that propofol at a therapeutic concentration can downregulate TNF-α biosynthesis possibly via inhibition of NFκB-mediated toll-like receptor 4 gene expression.

AB - Lipopolysaccharide (LPS), a gram-negative bacterial outer membrane component, can activate macrophages via a toll-like receptor 4-dependent pathway. Our previous study has shown that propofol, an intravenous anesthetic reagent, has anti-inflammatory effects. This study was further aimed to evaluate the roles of toll-like receptor 4 in propofol-caused suppression of tumor necrosis factor-α (TNF-α) biosynthesis in LPS-stimulated macrophages and its possible molecular mechanisms. Exposure of macrophages to propofol and LPS did not affect cell viability. Meanwhile, the LPS-caused augmentations in the productions of TNF-α protein and mRNA were significantly decreased following incubation with a therapeutic concentration of propofol (50 μM). Analysis of toll-like receptor 4 small interference (si)RNA revealed that this membrane receptor might participate in the propofol-caused suppression of TNF-α biosynthesis. Treatment of macrophages with LPS-induced toll-like receptor 4 protein and mRNA productions. Propofol at a clinically relevant concentration could inhibit such induction. In parallel, the LPS-induced translocation and transactivation of transcription factor nuclear factor-kappa B (NFκB) were significantly alleviated following propofol incubation. There are several NFκB DNA-binding motifs found in the promoter region of toll-like receptor 4. Therefore, this study shows that propofol at a therapeutic concentration can downregulate TNF-α biosynthesis possibly via inhibition of NFκB-mediated toll-like receptor 4 gene expression.

KW - LPS

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KW - TNF-α

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