Activated protein C inhibits lipopolysaccharide-induced nuclear translocation of nuclear factor kappaB (NF-kappaB) and tumour necrosis factor alpha (TNF-alpha) production in the THP-1 monocytic cell line

B White, M Schmidt, C Murphy, W Livingstone, D O'Toole, M Lawler, L O'Neill, D Kelleher, H P Schwarz, O P Smith, Mark Lawler

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212 Citations (Scopus)

Abstract

Activated protein C (APC) protects against sepsis in animal models and inhibits the lipopolysacharide (LPS)-induced elaboration of proinflammatory cytokines from monocytes. The molecular mechanism responsible for this property is unknown. We assessed the effect of APC on LPS-induced tumour necrosis factor alpha (TNF-alpha) production and on the activation of the central proinflammatory transcription factor nuclear factor-kappaB (NF-kappaB) in a THP-1 cell line. Cells were preincubated with varying concentrations of APC (200 microg/ml, 100 microg/ml and 20 microg/ml) before addition of LPS (100 ng/ml and 10 microg/ml). APC inhibited LPS-induced production of TNF-alpha both in the presence and absence of fetal calf serum (FCS), although the effect was less marked with 10% FCS. APC also inhibited LPS-induced activation of NF-kappaB, with APC (200 microg/ml) abolishing the effect of LPS (100 ng/ml). The ability of APC to inhibit LPS-induced translocation of NF-kappaB is likely to be a significant event given the critical role of the latter in the host inflammatory response.

Original languageEnglish
Pages (from-to)130-4
Number of pages5
JournalBritish Journal of Haematology
Volume110
Issue number1
Publication statusPublished - Jul 2000

Keywords

  • Analysis of Variance
  • Cell Line
  • Humans
  • Lipopolysaccharides
  • Monocytes
  • NF-kappa B
  • Protein C
  • Statistics, Nonparametric
  • Translocation, Genetic
  • Tumor Necrosis Factor-alpha

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