Human TFPI(Tissue factor pathway inhibitor) ELISA Kit

Hormone-sensitive cancers can be influenced by estrogens, a process usually mediated through the estrogen receptor (ER). Tissue factor pathway inhibitor type 2 (TFPI-2) is a Kunitz-type serine protease inhibitor involved in regulating the extracellular matrix. The present study demonstrates that the expression of TFPI-2 can be induced by estrogens. Breast cancer data from GOBO displayed increased levels of TFPI-2 and increased survival in patients with ER alpha+ tumors. Treatment of MCF7 cells (ERa+) with 17 beta-estradiol (E2) or 17 alpha-ethinyl estradiol (EE2) increased TFPI-2 mRNA and protein levels. This effect was mitigated with fulvestrant and by knocking down Ha, indicating that estrogen mediated TFPI-2 induction was through ER alpha. Upon knock down of DNA cytosine-5 methyltransferase 1 (DNMT1) or lysine-specific demethylase 1 (LSDI) in MCF7 cells, reduced effect of E2 on TFPI-2 mRNA levels was observed. Our data thus suggest that estrogen induced TFPI-2 expression in MCF7 cells is mediated by ERa and also by the action of LSDI. (C) 2017 Elsevier B.V. All rights reserved.

Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia. Coagulation and inflammation interact in the host response to infection. Tissue factor pathway inhibitor (TFPI) is a natural anticoagulant protein that inhibits tissue factor (IF), the main activator of inflammation-induced coagulation. It was the objective of this study to investigate the effect of endogenous TFPI levels on coagulation, inflammation and bacterial growth during S. pneumoniae pneumonia in mice. The effect of low endogenous TFPI levels was studied by administration of a neutralising anti-TFPI antibody to wild-type mice, and by using genetically modified mice expressing low levels of TFPI, due to a genetic deletion of the first Kunitz domain of TFPI (TFPIK1(-/-)) rescued with a human TFPI transgene. Pneumonia was induced by intranasal inoculation with S. pneumoniae and samples were obtained at 6, 24 and 48 hours after infection. Anti-TFPI reduced TFPI activity by similar to 50%. Homozygous lowTFPI mice and heterozygous controls had similar to 10% and similar to 50% of normal TFPI activity, respectively. TFPI levels did not influence bacterial growth or dissemination. Whereas lung pathology was unaffected in all groups, mice with similar to 10 % (but not with similar to 50%) of TFPI levels displayed elevated lung cytokine and chemokine concentrations 24 hours after infection. None of the groups with low TFPI levels showed an altered procoagulant response in lungs or plasma during pneumonia. These data argue against an important role for endogenous TFPI in the antibacterial, inflammatory and procoagulant response during pneumococcal pneumonia.