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.

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.

• Authors: B White, M Schmidt, C Murphy, W Livingstone, D O'Toole, M Lawler, L O'Neill, D Kelleher, H P Schwarz, O P Smith
• Journal: British journal of haematology (Br J Haematol) Vol. 110 Issue 1 Pg. 130-4 (Jul 2000) ISSN: 0007-1048 [Print] England
• PMID: 10930989 (Publication Type: Journal Article)

Chemical References

• Lipopolysaccharides
• NF-kappa B
• Protein C
• Tumor Necrosis Factor-alpha

Topics

• Analysis of Variance
• Cell Line
• Humans
• Lipopolysaccharides (pharmacology)
• Monocytes (drug effects, metabolism)
• NF-kappa B (genetics)
• Protein C (pharmacology)
• Statistics, Nonparametric
• Translocation, Genetic (drug effects)
• Tumor Necrosis Factor-alpha (biosynthesis)