PULMONARY TISSUE FACTOR mRNA EXPRESSION DURING MURINE TRAUMATIC SHOCK: EFFECT OF P-SELECTIN BLOCKADE

Shock ◽  
2001 ◽  
Vol 15 (4) ◽  
pp. 323-326 ◽  
Author(s):  
Valerie E. Armstead ◽  
Alexander G. Minchenko ◽  
Rosario Scalla ◽  
Allan M. Lefer
Keyword(s):  
Mrna Expression ◽  
Tissue Factor ◽  
Traumatic Shock ◽  
Pulmonary Tissue ◽  
Shock Effect

Tissue Factor Expression in Vital Organs during Murine Traumatic Shock 

1999 ◽  
Vol 91 (6) ◽  
pp. 1844-1844 ◽  
Author(s):  
Valerie E. Armstead ◽  
Irina L. Opentanova ◽  
Alexander G. Minchenko ◽  
Allan M. Lefer
Keyword(s):  
Small Intestine ◽  
Mrna Expression ◽  
Tissue Factor ◽  
Messenger Rna ◽  
Mrna Level ◽  
Regulatory Elements ◽  
Traumatic Shock ◽  
Surface Glycoprotein ◽  
Cell Surface Glycoprotein ◽  
Nf Kappab

Background Tissue factor (TF) is a cell-surface glycoprotein responsible for initiating the extrinsic pathway of coagulation that has been shown to have a role in the pathophysiology of sepsis and reperfusion injury. The purpose of this study was to investigate TF expression in vital organs and to determine possible regulatory mechanisms of TF expression in the lung during traumatic shock in rats. Methods Noble-Collip drum trauma was induced in anesthetized Sprague-Dawley rats. Anesthetized rats without trauma served as controls. TF activity was measured in plasma and lung tissue. TF messenger RNA (mRNA) was measured in the lung, liver, and small intestine using ribonuclease protection assays. Electromobility shift assays were used to quantify binding of nuclear extracts from lung to TF-specific consensus domains for transcription factors NF-kappaB and AP-1. Results TF activity in plasma increased up to 14-fold and +232% in the lung (P < 0.001 for plasma and lung) 2 h after trauma. TF mRNA level was significantly increased in the lungs (P < 0.01), small intestine (P < 0.01), and liver (P < 0.05) 1 h after trauma compared to sham-operated control rats. TF mRNA expression continued to increase in the lungs and the liver (both, P < 0.001) 2 h after trauma TF sequence-specific complex binding to AP-1 and NF-kappaB domains was enhanced in the lungs of trauma rats (+395%, P < 0.001 and +168%, P < 0.001, respectively). Conclusions These results suggest that TF may play an important role in the pathophysiology of severe trauma and that regulatory elements AP-1 and NF-kappaB may be involved in the regulation of TF mRNA expression in traumatic shock.

Heme Oxygenase-1 mRNA Expression in the Lung during Murine Traumatic Shock: Effect of rsPSGL.1g

2002 ◽  
Vol 96 (Sup 2) ◽  
pp. A420
Author(s):  
Alexander G. Minchenko ◽  
Irina L. Opentanova ◽  
Valerie E. Armstead
Keyword(s):  
Mrna Expression ◽  
Heme Oxygenase ◽  
Traumatic Shock ◽  
Heme Oxygenase 1 ◽  
Shock Effect

scholarly journals Upregulation of pulmonary tissue factor, loss of thrombomodulin and immunothrombosis in SARS-CoV-2 infection

2021 ◽  
Vol 39 ◽  
pp. 101069
Author(s):  
Ivo M.B. Francischetti ◽  
Kevin Toomer ◽  
Yifan Zhang ◽  
Jayesh Jani ◽  
Zishan Siddiqui ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Pulmonary Tissue

Abstract 805: Differential Regulation Of Cytokine-induced Alternative Splicing Of The TF Gene By Serine/Arginine Rich Protein Kinases

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Ursula Rauch ◽  
Andreas Eisenreich ◽  
Wolfgang Poller ◽  
Heinz-Peter Schultheiss
Keyword(s):  
Alternative Splicing ◽  
Protein Phosphorylation ◽  
Mrna Expression ◽  
Tissue Factor ◽  
Splice Variant ◽  
Sr Protein ◽  
Phosphorylation State ◽  
Post Induction ◽  
Tnf Α ◽  
Tf Gene

Background: Higher eukaryotes control gene expression and increase protein diversity by alternative splicing of pre-mRNA. The Cdc2-like kinase (Clk) family, DNA topoisomerase I (DNA topo I) or Akt kinase are involved in splicing control by regulating the phosphorylation state of serine/arginine rich (SR) proteins. We recently showed that alternatively spliced human tissue factor (asHTF), a soluble isoform of tissue factor (TF), the primary initiator of coagulation, is expressed in HUVECs in response to inflammatory cytokines. This study investigated the role of Clks, DNA topo I and the PI3K-Pathway in regulation of TF-splicing in TNF-α induced HUVECs. Methods: HUVECs were incubated with inhibitors of Clks, DNA-topo I or PI3K and were then stimulated with TNF-α. The SR protein phosphorylation state was determined 2 min post induction. The full length (fl) TF and asHTF mRNA were assessed 60 min post induction by Real-Time PCR. Proteins were measured 5 and 8 hours after stimulation by Western blots and the cell thrombogenicity was analyzed via a chromogenic assay. Results: TNF-α inceased the mRNA expression of asHTF and flTF in HUVECs. The Clk-inhibitor completely inhibited the TNF-α induced expression of asHTF and reduced flTF by 30 %. Inhibition of DNA topo I increased asHTF expression and reduced the flTF expression. Inhibition of the PI3K/Akt-pathway had no effect on TF mRNA expression. Reduced Clk-inhibition the TF activity by 50 % whereas DNA topo I inhibition significantly decreased the procoagulant TF activity 8 hours post TNF-α induction. The Clk- and DNA-topo I-inhibitors altered the SR-protein phosphorylation pattern post TNF-α-induction. Additionally resulted inhibition of Clks in the generation of a third TF mRNA-splice variant, TF-A. Conclusion: Selective inhibition of Clks or DNA topo I leads to alterations of SR-protein phosphorylation and affects the differential expression of TF isoforms, thereby modulating the thrombogenicity of HUVECs. The inhibition of Clks contributes to the generation of a third TF splice variant. The inhibition of these kinases gives new insights into the regulation of the TF gene splicing process, which may result in new therapeutic strategies for modulating cellular thrombogenicity.

Lysophosphatidylcholine Decreases the Synthesis of Tissue Factor Pathway Inhibitor in Human Umbilical Vein Endothelial Cells

1998 ◽  
Vol 79 (01) ◽  
pp. 217-221 ◽  
Author(s):  
Koichi Kokame ◽  
Toshiyuki Miyata ◽  
Naoaki Sato ◽  
Hisao Kato
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Umbilical Vein ◽  
Mrna Levels ◽  
Down Regulation ◽  
Human Umbilical Vein ◽  
Tissue Factor Pathway ◽  
Umbilical Vein Endothelial Cells

SummaryThrombotic complications are frequently associated with atherosclerosis. Lysophosphatidylcholine (LPC), a component accumulated in oxidatively modified LDL (ox-LDL), is known to play a crucial role in the initiation and progression of atherosclerotic vascular lesions. Since a vascular anticoagulant, tissue factor pathway inhibitor (TFPI), has the function of regulating the initial reaction of tissue factor (TF)-induced coagulation, we investigated the effect of LPC on TFPI synthesis in cultured human umbilical vein endothelial cells (HUVEC). The treatment of HUVEC with LPC for 24 h decreased TFPI antigen levels in both the culture medium and the cell lysate in a dose-dependent manner. Northern blot analysis revealed that LPC caused a time-dependent decrease in the TFPI mRNA levels. The levels of TFPI antigen and mRNA were decreased to 72% and 38%, respectively, by the incubation with 50 μM LPC for 24 h. The down-regulation by LPC of TFPI mRNA expression was not observed in the presence of cycloheximide, suggesting that protein synthesis was involved in the suppression of TFPI mRNA expression. The TFPI mRNA levels in actinomycin D-treated cells were relatively stable, indicating that the down-regulation of TFPI mRNA by LPC would be partly explained by the enhanced mRNA destabilization. In contrast to the significant down-regulatory effects of LPC on TFPI expression, LPC did not induce TF mRNA expression in HUVEC. These results indicate that LPC accumulated in the atherosclerotic vascular wall would suppress endothelial TFPI synthesis, reducing the antithrombotic property of endothelial cells.

scholarly journals Oncostatin M promotes biphasic tissue factor expression in smooth muscle cells: evidence for Erk-1/2 activation

Blood ◽  
2001 ◽  
Vol 97 (3) ◽  
pp. 692-699 ◽  
Author(s):  
Toshiya Nishibe ◽  
Graham Parry ◽  
Atsushi Ishida ◽  
Salim Aziz ◽  
Jacqueline Murray ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Dna Binding ◽  
Smooth Muscle Cells ◽  
Mrna Expression ◽  
Tissue Factor ◽  
Muscle Cells ◽  
Binding Activity ◽  
Oncostatin M ◽  
Dna Binding Activity ◽  
Atherosclerotic Lesions

Abstract Tissue factor (TF), a transmembrane glycoprotein, initiates the extrinsic coagulation cascade. TF is known to play a major role in mediating thrombosis and thrombotic episodes associated with the progression of atherosclerosis. Macrophages at inflammatory sites, such as atherosclerotic lesions, release numerous cytokines that are capable of modulating TF expression. This study examined the role of oncostatin M (OSM), a macrophage/ T-lymphocyte–restricted cytokine, in the expression of TF in vascular smooth muscle cells (SMCs). It is reported here that OSM stimulated a biphasic and sustained pattern of TF messenger RNA (mRNA). The effect of OSM on TF mRNA expression was regulated at the transcriptional level as determined by nuclear run-offs and transient transfection of a TF promoter-reporter gene construct. OSM-induced TF expression was regulated primarily by the transcription factor NF-κB. Activation of NF-κB by OSM did not require IκB-α degradation. Inhibition of MEK activity by U0126 prevented OSM-induced TF expression by suppressing NF-κB DNA binding activity as determined by gel-shift analysis. Further, inhibition of Erk-1/2 protein by antisense treatment resulted in suppression of TF mRNA expression, indicating a role for Erk-1/2 in modulating NF-κB DNA binding activity. These studies suggest that the induced expression of TF by OSM is primarily through the activation of NF-κB and that activation of NF-κB is regulated in part by the MEK/Erk-1/2 signal transduction pathway. This study indicates that OSM may play a key role in promoting TF expression in SMCs within atherosclerotic lesions.

A selective defect in tissue factor mRNA expression in monocytes from AIDS patients

1990 ◽  
Vol 54 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Janet L. Lathey ◽  
Jan M. Agosti ◽  
Jay A. Nelson ◽  
Lawrence Corey ◽  
Susan A. Gregory ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Tissue Factor ◽  
Aids Patients

Modulation of tissue factor expression by rapamycin and FK-506 in lipopolysaccharide-stimulated human mononuclear cells and serum-stimulated aortic smooth muscle cells

2005 ◽  
Vol 94 (07) ◽  
pp. 46-52 ◽  
Author(s):  
Soumeya Hammal ◽  
Nejma Ameziane ◽  
Marie-Thérèse Labro ◽  
Dominique de Prost ◽  
Véronique Ollivier
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mrna Expression ◽  
Tissue Factor ◽  
Mononuclear Cells ◽  
Muscle Cells ◽  
Monocytic Cells ◽  
Fk 506 ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle

SummaryInflammation is a key pathogenic component of atherosclerosis; it also promotes thrombosis, a process underlying acute coronary events and stroke. Cells present in atherosclerotic plaque show abnormal tissue factor (TF) expression. Macrolides, in addition to their antimicrobial properties, have antiinflammatory effects that might help prevent atherothrombosis. The aim of this study was to determine the effect of an immunosuppressant macrolide, rapamycin (Sirolimus), on the expression of TF and its inhibitor (TFPI) by monocytic cells (human blood mononuclear and THP-1 cells) and human aortic smooth muscle cells, in comparison with FK-506 and azithromycin. In monocytic cells, rapamycin and FK-506 inhibited LPS-induced TF activity, antigen and mRNA expression through a transcriptional mechanism involving NF-κB. In smooth muscle cells, rapamycin and azithromycin had no effect on serum-induced TF expression, while FK-506 increased serum-induced TF protein and mRNA expression. TFPI levels in the culture supernatants of serum-stimulated smooth muscle cells were not modified by any of the three macrolides. Rapamycin slightly inhibits TFPI induction by LPS in monocytic cells. In addition to its recently established efficacy in the prevention of stent restenosis, the inhibitory effect of rapamycin on theTF pathway might have interesting therapeutic implications.

scholarly journals Tissue factor mRNA expression in the endothelium of an intact umbilical vein

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 174-179 ◽  
Author(s):  
MA Courtney ◽  
PJ Haidaris ◽  
VJ Marder ◽  
LA Sporn
Keyword(s):  
Endothelial Cells ◽  
In Situ Hybridization ◽  
Endothelial Cell ◽  
Mrna Expression ◽  
Tissue Factor ◽  
Umbilical Vein ◽  
Spotted Fever ◽  
Vascular Endothelial Cell ◽  
Immunocytochemical Staining

Abstract Tissue factor (TF) mRNA expression was measured by in situ hybridization in the endothelium of the intact human umbilical vein after infection with Rickettsia rickettsii. At 4 hours, R rickettsii organisms were clearly visible within approximately 70% of endothelial cells by immunocytochemical staining. Quantitation of TF mRNA expression revealed that the level within endothelial cells of the infected vein was significantly greater (3.7-fold, P < .0001) than that detected in uninfected endothelial cells. Serial sections of the umbilical cord vein were processed for in situ hybridization, and immunocytochemical staining and showed TF expression in those endothelial cells that contained R rickettsii organisms. Immunocytochemical staining for TF antigen at 6 hours was negative, but TF was clearly demonstrated within macrophages and fibroblasts of both control and infected umbilical cords. These studies demonstrate that the vascular endothelial cell, ex vivo, can be directly induced to express TF mRNA. This observation has not heretofore been clearly demonstrated except for in cultured endothelial cells. Since R rickettsii infection induces thrombotic vascular occlusions in patients with Rocky Mountain Spotted Fever, the results imply a potential role for endothelial cell TF in the pathogenesis of thrombotic disease.

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