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- Title
Activated protein C inhibits lipopolysaccharide-induced nuclear translocation of nuclear factor κB (NF-κB) and tumour necrosis factor α (TNF-α) production in the THP-1 monocytic cell line.
- Authors
White, B.; Schmidt, M.; Murphy, C.; Livingstone, W.; O'Toole, D.; Lawler, M.; O'Neill, L.; Kelleher, D.; Schwarz, H. P.; Smith, O. P.
- 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 α (TNF-α) production and on the activation of the central proinflammatory transcription factor nuclear factor-κB (NF-κB) in a THP-1 cell line. Cells were preincubated with varying concentrations of APC (200 µg/ml, 100 µg/ml and 20 µg/ml) before addition of LPS (100 ng/ml and 10 µg/ml). APC inhibited LPS-induced production of TNF-α 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-κB, with APC (200 µg/ml) abolishing the effect of LPS (100 ng/ml). The ability of APC to inhibit LPS-induced translocation of NF-κB is likely to be a significant event given the critical role of the latter in the host inflammatory response.
- Subjects
PROTEIN C; ENDOTOXINS; TUMOR necrosis factors; CYTOKINES; MONOCYTES; CHEMICAL inhibitors; BIOCHEMICAL mechanism of action; PHYSIOLOGY
- Publication
British Journal of Haematology, 2000, Vol 110, Issue 1, p130
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1046/j.1365-2141.2000.02128.x