These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Shiga toxin downregulates tissue factor pathway inhibitor, modulating an increase in the expression of functional tissue factor on endothelium.
    Author: Grabowski EF, Kushak RI, Liu B, Ingelfinger JR.
    Journal: Thromb Res; 2013 Jun; 131(6):521-8. PubMed ID: 23642803.
    Abstract:
    INTRODUCTION: Endothelial expression of tissue factor (TF) may play a major role in (Stx)-related hemolytic uremic syndrome. We examined human umbilical vein endothelial cell (HUVEC) monolayers to determine the interaction between TF and TF pathway inhibitor (TFPI), hypothesizing that changes in TFPI modulate TF expression. MATERIALS AND METHODS: We studied 1) cell surface expression of globotriasylceramide (Gb3, the receptor for Stx) with Stx-1 (10 pM), TNFα (20 Ng/ml), or Stx-1 plus TNFα compared to control, 2) gene expression of TF and TFPI, 3) total cellular and cell surface antigenic TF and TFPI, 4) TFPI secretion into supernatant, and 5) factor Xa production. RESULTS AND CONCLUSIONS: Gb3 expression, negligible with control and Stx-1 alone, increased significantly with TNFα and with Stx-1 plus TNFα. TF mRNA increased 1.25 ± 0.32- fold (N = 9; p = 0.041) with Stx-1 alone vs. 2.82 ± 0.92-fold (N = 13; p < 0.0005) with TNFα alone. However, Stx-1 plus TNFα yielded a 6.51 ± 3.48-fold increase (N = 17; p < 0.0005). TFPI mRNA decreased with TNFα (p < 0.001) and Stx-1 plus TNFα (p < 0.0005). Total cellular and cell surface TF antigen increased significantly with TNFα, but no further with Stx-1 plus TNFα. Total TFPI cellular and cell surface antigen levels, and TFPI secretion decreased significantly with Stx-1 plus TNFα. Median factor Xa production for Stx-1 plus TNFα vs TNFα alone increased (p < 0.001) 3.24-fold. Our results indicate that a subinhibitory concentration of Stx-1 plus TNFα impairs TFPI gene expression, synthesis, cell-surface association, and secretion, leading to augmented functional TF.
    [Abstract] [Full Text] [Related] [New Search]