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.

scholarly journals Obesity May Provide Pro-ILC3 Development Inflammatory Environment in Asthmatic Children

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Yumin Wu ◽  
Jiawei Yue ◽  
Juncheng Wu ◽  
Wei Zhou ◽  
Dapeng Li ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Messenger Rna ◽  
Mrna Level ◽  
Asthma Severity ◽  
Lymphoid Cells ◽  
Mrna Levels ◽  
Asthmatic Children ◽  
Prevalence Of Obesity ◽  
Elevated Frequency ◽  
Relative Mrna Expression

The prevalence of obesity in children has dramatically increased in the last few decades, and obesity has also emerged as an important risk factor for asthma. Innate mechanisms have been shown to be involved in both diseases, particularly through the recently described innate lymphoid cells (ILCs), in which ILC3s have been linked to obesity both in human and in murine models. The aim of this study was to explore whether being overweight in asthmatic children was associated with elevated circulating ILC3 or elevated messenger RNA (mRNA) levels of RORC, IL-17A, and IL-22. Our results showed significantly elevated ILC3 frequencies in overweight asthmatic children compared with nonoverweight controls based on the detection of Lin+CD127+IL-23R+ cells by flow cytometry. Moreover, elevated ILC3 frequencies positively correlated with the mRNA expression of RORC which has been identified as a transcription factor of ILC3s. The relative mRNA expression level of IL-17A was also upregulated in overweight compared to nonoverweight children, as was the relative mRNA level of IL-22. However, there were no correlations between ILC3 frequencies or the expressions of RORC, IL-17A, and IL-22 and asthma severity. These results suggested that childhood obesity is an independent factor that is associated with an elevated frequency of circulating ILC3s and higher expressions of RORC, IL-22, and IL-17A.

Effect of resveratrol analogue, DMU-212, on antioxidant status and apoptosis-related genes in rat model of hepatocarcinogenesis

2016 ◽  
Vol 36 (2) ◽  
pp. 160-175 ◽  
Author(s):  
H Piotrowska ◽  
M Kujawska ◽  
M Nowicki ◽  
E Petzke ◽  
E Ignatowicz ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Mrna Expression ◽  
Messenger Rna ◽  
Mrna Level ◽  
Combined Treatment ◽  
Antioxidant Properties ◽  
Thiobarbituric Acid ◽  
Protein Carbonyls ◽  
Genes Encoding ◽  
Male Wistar Rats

The aim of the study was to examine whether antioxidant properties of 3,4,4′,5-tetramethoxystilbene (DMU-212) contribute to its anticarcinogenic activity and whether DMU-212 affects the expression of apoptosis-related genes. Two-stage model of hepatocarcinogenesis was used; male Wistar rats were challenged with N-nitrosodiethylamine (NDEA), 200 mg/kg body weight (b.w.), intraperitoneal, then phenobarbital (PB) in drinking water (0.05%) was administered. Simultaneously, DMU-212 was given per os at a dose 20 or 50 mg/kg b.w. two times a week for 16 weeks. DMU-212 caused a moderate decrease in hepatic thiobarbituric acid reactive substances and protein carbonyls concentration elevated in rats treated with NDEA/PB. The activity of antioxidant enzymes examined reduced by NDEA/PB treatment was not restored in rats coadministered with DMU-212. Effects of DMU-212 on messenger RNA (mRNA) expression of antioxidant enzymes in rats challenged with NDEA/PB were diversified; no changes in their protein expression were noted in any of the groups. The expression of 17,000 genes was analyzed by Affymetrix® Rat Gene 1.1 ST Array; 15 apoptosis-related genes were selected and validated by RT-q PCR. The combined treatment with NDEA/PB and DMU-212 increased the mRNA level of some genes driving mitochondria-mediated apoptosis, whereas the mRNA expression of some anti-apoptotic genes triggering receptor-mediated apoptosis was reduced. The expression of genes encoding caspases-4, -8, -9, and -12 was also increased in rats treated with DMU-212. Although antioxidant effect of DMU-212 in rats challenged with NDEA/PB was moderate, its potential anticarcinogenic properties were demonstrated as evidenced by modulation of apoptosis-related genes.

scholarly journals NFAT promotes carcinoma invasive migration through glypican-6

2011 ◽  
Vol 440 (1) ◽  
pp. 157-166 ◽  
Author(s):  
Gary K. Yiu ◽  
Aura Kaunisto ◽  
Y. Rebecca Chin ◽  
Alex Toker
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Regulatory Elements ◽  
Surface Glycoprotein ◽  
Mitogen Activated Protein Kinase ◽  
Proximal Promoter ◽  
Activated T Cells ◽  
Cell Surface Glycoprotein

Invasive migration of carcinoma cells is a prerequisite for the metastatic dissemination of solid tumours. Numerous mechanisms control the ability of cancer cells to acquire a motile and invasive phenotype, and subsequently degrade and invade the basement membrane. Several genes that are up-regulated in breast carcinoma are responsible for mediating the metastatic cascade. Recent studies have revealed that the NFAT (nuclear factor of activated T-cells) is a transcription factor that is highly expressed in aggressive breast cancer cells and tissues, and mediates invasion through transcriptional induction of pro-invasion and migration genes. In the present paper we demonstrate that NFAT promotes breast carcinoma invasion through induction of GPC (glypican) 6, a cell-surface glycoprotein. NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype. The mechanism by which GPC6 promotes invasive migration involves inhibition of canonical β-catenin and Wnt signalling, and up-regulation of non-canonical Wnt5A signalling leading to the activation of JNK (c-Jun N-terminal kinase) and p38 MAPK (mitogen-activated protein kinase). Thus GPC6 is a novel NFAT target gene in breast cancer cells that promotes invasive migration through Wnt5A signalling.

The in vivo kinetics of tissue factor messenger RNA expression during human endotoxemia: relationship with activation of coagulation

Blood ◽  
2000 ◽  
Vol 96 (2) ◽  
pp. 554-559 ◽  
Author(s):  
Rendrik F. Franco ◽  
Evert de Jonge ◽  
Pascale E. P. Dekkers ◽  
Janneke J. Timmerman ◽  
C. Arnold Spek ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Tissue Factor ◽  
Messenger Rna ◽  
Thrombin Generation ◽  
Mrna Levels ◽  
Total Blood ◽  
Human Endotoxemia ◽  
Lps Challenge ◽  
Kinetics Of

Abstract Triggering of the tissue factor (TF)-dependent coagulation pathway is considered to underlie the generation of a procoagulant state during endotoxemia. To determine the in vivo pattern of monocytic TF messenger RNA (mRNA) expression during endotoxemia, 10 healthy volunteers were injected with lipopolysaccharide (LPS, 4 ng/kg) and blood was collected before and 0.5, 1, 2, 3, 4, 6, 8, and 24 hours after LPS administration. Total blood RNA was isolated and amplified by NASBA (nucleic acid sequence-based amplification), followed by quantitation of TF mRNA by an electrochemiluminescence (ECL) assay. To compare the pattern of coagulation activation with the kinetics of monocytic TF mRNA expression, we measured plasma levels of markers of thrombin generation, thrombin-antithrombin (TAT) complexes, and prothrombin fragment 1 + 2 (F1 + 2). Baseline value (mean ± SEM) of the number of TF mRNA molecules per monocytic cell was 0.08 ± 0.02. A progressive and significant (P < .0001) increase in TF expression was observed after LPS injection (+0.5 hour: 0.3 ± 0.1, +1 hour: 1.3 ± 0.9, +2 hours: 4.1 ± 0.9), peaking at +3 hours (10 ± 1.9 TF mRNA molecules per monocyte). As TF mRNA levels increased, thrombin generation was augmented. Peak levels of TAT and F1 + 2 were reached later (at t +4 hours) than those of TF mRNA. TF mRNA, TAT, and F1 + 2 levels returned to baseline after 24 hours. In conclusion, we used a NASBA/ECL-based technique to quantify TF mRNA in whole blood during human endotoxemia and observed a 125-fold increase in TF mRNA levels. Our data demonstrate a pivotal role for enhanced TF gene activity in the activation of coagulation after LPS challenge.

scholarly journals CDO: An Oncogene-, Serum-, and Anchorage-regulated Member of the Ig/Fibronectin Type III Repeat Family

1997 ◽  
Vol 138 (1) ◽  
pp. 203-213 ◽  
Author(s):  
Jong-Sun Kang ◽  
Min Gao ◽  
Jessica L. Feinleib ◽  
Philip D. Cotter ◽  
Sarah N. Guadagno ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Surface Glycoprotein ◽  
Rat Tissues ◽  
Mrna Levels ◽  
Cell Surface Glycoprotein ◽  
Type Iii ◽  
Extracellular Region ◽  
Ig Superfamily ◽  
Fibronectin Type Iii ◽  
Fibronectin Type

Cell adhesion molecules of the Ig superfamily are implicated in a wide variety of biological processes, including cell migration, axon guidance and fasciculation, and growth control and tumorigenesis. Expression of these proteins can be highly dynamic and cell type specific, but little is known of the signals that regulate such specificity. Reported here is the molecular cloning and characterization of rat CDO, a novel cell surface glycoprotein of the Ig superfamily that contains five Ig-like repeats, followed by three fibronectin type III–like repeats in its extracellular region, and a 256-amino acid intracellular region that does not resemble other known proteins. In rat embryo fibroblasts, cdo mRNA expression is maximal in confluent, quiescent cells. It is rapidly and transiently down-regulated by serum stimulation of such cells, and is constitutively down-regulated in oncogene-transformed derivatives of these cells. CDO protein levels are also dramatically regulated by cell–substratum adhesion, via a mechanism that is independent of cdo mRNA expression. The amount of CDO produced at the surface of a cell may therefore be governed by a complex balance of signals, including mitogenic stimuli that regulate cdo mRNA levels, and substratum-derived signals that regulate CDO protein production. cdo mRNA is expressed at low levels in most adult rat tissues. A closely related human gene maps to chromosome 11q23–24, a region that displays frequent loss of heterozygosity in human lung, breast, and ovarian tumors. Taken together, these data suggest that loss of CDO function could play a role in oncogenesis.

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

scholarly journals Bone Immune Response to Materials, Part I: Titanium, PEEK and Copper in Comparison to Sham at 10 Days in Rabbit Tibia

2018 ◽  
Vol 7 (12) ◽  
pp. 526 ◽  
Author(s):  
Ricardo Trindade ◽  
Tomas Albrektsson ◽  
Silvia Galli ◽  
Zdenka Prgomet ◽  
Pentti Tengvall ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Activation ◽  
Bone Growth ◽  
Mrna Level ◽  
Titanium Implants ◽  
Surface Glycoprotein ◽  
Macrophage Phenotype ◽  
Cell Surface Glycoprotein ◽  
Rabbit Tibia ◽  
M2 Phenotype

Bone anchored biomaterials have become an indispensable solution for the restoration of lost dental elements and for skeletal joint replacements. However, a thorough understanding is still lacking in terms of the biological mechanisms leading to osseointegration and its contrast, unwanted peri-implant bone loss. We have previously hypothesized on the participation of immune mechanisms in such processes, and later demonstrated enhanced bone immune activation up to 4 weeks around titanium implants. The current experimental study explored and compared in a rabbit tibia model after 10 days of healing time, the bone inflammation/immunological reaction at mRNA level towards titanium, polyether ether ketone (PEEK) and copper compared to a Sham control. Samples from the test and control sites were, after a healing period, processed for gene expression analysis (polymerase chain reaction, (qPCR)) and decalcified histology tissue analysis. All materials displayed immune activation and suppression of bone resorption, when compared to sham. The M1 (inflammatory)/M2 (reparative) -macrophage phenotype balance was correlated to the proximity and volume of bone growth at the implant vicinity, with titanium demonstrating a M2-phenotype at 10 days, whereas copper and PEEK were still dealing with a mixed M1- and M2-phenotype environment. Titanium was the only material showing adequate bone growth and proximity inside the implant threads. There was a consistent upregulation of (T-cell surface glycoprotein CD4) CD4 and downregulation of (T-cell transmembrane glycoprotein CD8) CD8, indicating a CD4-lymphocyte phenotype driven reaction around all materials at 10 days.

Local Anesthetics Inhibit Tissue Factor Expression in Activated Monocytes via Inhibition of Tissue Factor mRNA Synthesis

2010 ◽  
Vol 17 (6) ◽  
pp. E4-E9 ◽  
Author(s):  
Ji-Eun Kim ◽  
Ki Jun Kim ◽  
Wonsik Ahn ◽  
Kyou-Sup Han ◽  
Hyun Kyung Kim
Keyword(s):  
Tissue Factor ◽  
Local Anesthetics ◽  
Messenger Rna ◽  
Mrna Level ◽  
Dependent Manner ◽  
Tissue Factor Expression ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Factor Expression ◽  
Activated Monocytes

Local anesthetics have been reported to have anticoagulant properties, but the mechanisms responsible for this action are poorly understood. Here, we evaluated the in vitro effects of 3 local anesthetics—lidocaine, ropivacaine, and bupivacaine—on the tissue factor expression by monocytes. Monocytes from peripheral blood were stimulated with lipopolysaccharide (LPS) in the presence or absence of local anesthetics. All 3 local anesthetics inhibited the expression of tissue factor antigen and tissue factor activity in LPS-stimulated monocytes in a dose- and time-dependent manner and reduced tissue factor messenger RNA (mRNA) expression in endothelial cells and a monocytic cell line. None of the 3 drugs induced apoptosis or affected the viability of monocytes. Our findings that local anesthetics inhibited the tissue factor induction in activated monocytes by inhibiting tissue factor mRNA level may demonstrate the feasibility of using local anesthetics in hypercoagulable and inflammatory conditions.

The in vivo kinetics of tissue factor messenger RNA expression during human endotoxemia: relationship with activation of coagulation

Blood ◽  
2000 ◽  
Vol 96 (2) ◽  
pp. 554-559 ◽  
Author(s):  
Rendrik F. Franco ◽  
Evert de Jonge ◽  
Pascale E. P. Dekkers ◽  
Janneke J. Timmerman ◽  
C. Arnold Spek ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Tissue Factor ◽  
Messenger Rna ◽  
Thrombin Generation ◽  
Mrna Levels ◽  
Total Blood ◽  
Human Endotoxemia ◽  
Lps Challenge ◽  
Kinetics Of

Triggering of the tissue factor (TF)-dependent coagulation pathway is considered to underlie the generation of a procoagulant state during endotoxemia. To determine the in vivo pattern of monocytic TF messenger RNA (mRNA) expression during endotoxemia, 10 healthy volunteers were injected with lipopolysaccharide (LPS, 4 ng/kg) and blood was collected before and 0.5, 1, 2, 3, 4, 6, 8, and 24 hours after LPS administration. Total blood RNA was isolated and amplified by NASBA (nucleic acid sequence-based amplification), followed by quantitation of TF mRNA by an electrochemiluminescence (ECL) assay. To compare the pattern of coagulation activation with the kinetics of monocytic TF mRNA expression, we measured plasma levels of markers of thrombin generation, thrombin-antithrombin (TAT) complexes, and prothrombin fragment 1 + 2 (F1 + 2). Baseline value (mean ± SEM) of the number of TF mRNA molecules per monocytic cell was 0.08 ± 0.02. A progressive and significant (P < .0001) increase in TF expression was observed after LPS injection (+0.5 hour: 0.3 ± 0.1, +1 hour: 1.3 ± 0.9, +2 hours: 4.1 ± 0.9), peaking at +3 hours (10 ± 1.9 TF mRNA molecules per monocyte). As TF mRNA levels increased, thrombin generation was augmented. Peak levels of TAT and F1 + 2 were reached later (at t +4 hours) than those of TF mRNA. TF mRNA, TAT, and F1 + 2 levels returned to baseline after 24 hours. In conclusion, we used a NASBA/ECL-based technique to quantify TF mRNA in whole blood during human endotoxemia and observed a 125-fold increase in TF mRNA levels. Our data demonstrate a pivotal role for enhanced TF gene activity in the activation of coagulation after LPS challenge.

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