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TLR9 signaling regulates tissue factor and tissue factor pathway inhibitor expression and activity in human coronary artery endothelial cells
Author(s) -
El Kebir Driss,
Filep Janos G
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.835.4
Subject(s) - tissue factor , tlr9 , tissue factor pathway inhibitor , cpg site , dna methylation , biology , microbiology and biotechnology , dna , transcription (linguistics) , gene expression , gene , medicine , biochemistry , coagulation , linguistics , philosophy
Although human endothelial cells recognize and respond to bacterial DNA (CpG DNA), the role of bacterial DNA in procoagulation is not known. We investigated the impact of bacterial DNA on expression and activity of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in human coronary artery endothelial cells (HCAEC). CpG DNA (1–32 μg/ml) markedly induced TF expression between 4 and 8 hours in both protein and mRNA levels and TF activity. CpG DNA markedly enhanced NF‐êB activation, which was blocked by the telomere‐derived TLR9 antagonist oligonucleotide TTAGGG. Consistently, the specific NF‐êB inhibitors BAY 117082 and SN50 prevented CpG DNA‐induced TF transcription and secretion. Conversely, culture of HCAEC with CpG DNA for 24 to 48 hours reduced TFPI transcription, secretion, and activity. Methylation of cytosines in CpG DNA resulted in a complete loss of biological activities. Our results demonstrate that bacterial DNA through TLR9 can alter the balance of TF and TFPI expression and activity in HCAEC, thereby contributing to thrombus formation, the major cause of acute coronary artery disease.(Grant support: CIHR MOP‐97742).