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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
Author(s) -
White B.,
Schmidt M.,
Murphy C.,
Livingstone W.,
O'Toole D.,
Lawler M.,
O'Neill L.,
Kelleher D.,
Schwarz H. P.,
Smith O. P.
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.02128.x
Subject(s) - proinflammatory cytokine , tumor necrosis factor alpha , lipopolysaccharide , nf κb , nfkb1 , thp1 cell line , transcription factor , chromosomal translocation , biology , cell culture , monocyte , microbiology and biotechnology , chemistry , inflammation , endocrinology , medicine , immunology , biochemistry , genetics , gene
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.