scholarly journals Antibodies cross-reactive with E- and P-selectin block both E- and P- selectin functions

Blood ◽  
1995 ◽  
Vol 85 (1) ◽  
pp. 31-37 ◽  
Author(s):  
EL Berg ◽  
C Fromm ◽  
J Melrose ◽  
N Tsurushita
Keyword(s):  
Cell Lines ◽  
Therapeutic Potential ◽  
Umbilical Vein ◽  
Selection Criterion ◽  
Homologous Proteins ◽  
Necrosis Factor Alpha ◽  
Blocking Antibody ◽  
Inflammatory Conditions ◽  
Factor Alpha ◽  
Umbilical Vein Endothelial Cells

E- and P-selectin are inflammation-induced cell adhesion molecules that mediate leukocyte-endothelial cell and leukocyte-platelet interactions. Monoclonal antibodies (MoAbs) specific for either E-selectin or P- selectin are protective in several animal models of inflammatory disease. To generate an MoAb with broader therapeutic potential, MoAbs that bind to both E- and P-selectin were generated by immunization of mice with mouse pre-B cell lines transfected with human E- and P- selectin. Interestingly, although the only selection criterion was the ability to bind both E- and P-selectin, all three antibodies obtained efficiently block both E- and P-selectin-mediated functions. The inhibited functions include neutrophil or HL-60 cell binding to tumor necrosis factor-alpha-activated human umbilical vein endothelial cells, E- or P-selectin transfectant cell lines, and platelet-HL-60 rosetting. These antibodies, EP-5C7, EP-2C9, and EP-1D8, recognize the same or overlapping epitope within the lectin domains of E- and P-selectin. The data suggest that functionally important epitopes of homologous proteins can be targeted by selecting for antibodies with reactivity toward both proteins. Furthermore, a potent blocking antibody specific for both E- and P-selectin may provide a more effective and broadly useful reagent for treating acute and potentially certain chronic inflammatory conditions.

scholarly journals LINC00341 exerts an anti-inflammatory effect on endothelial cells by repressing VCAM1

2017 ◽  
Vol 49 (7) ◽  
pp. 339-345 ◽  
Author(s):  
Tse-Shun Huang ◽  
Kuei-Chun Wang ◽  
Sara Quon ◽  
Phu Nguyen ◽  
Ting-Yu Chang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Rna Seq ◽  
Necrosis Factor Alpha ◽  
Polycomb Repressive Complex 2 ◽  
Health And Disease ◽  
Factor Alpha ◽  
Anti Inflammatory ◽  
Umbilical Vein Endothelial Cells ◽  
Cell Adhesion Molecule 1

The long noncoding RNAs (lncRNAs), which constitute a large portion of the transcriptome, have gained intense research interest because of their roles in regulating physiological and pathophysiological functions in the cell. We identified from RNA-Seq profiling a set of lncRNAs in cultured human umbilical vein endothelial cells (HUVECs) that are differentially regulated by atheroprotective vs. atheroprone shear flows. Among the comprehensively annotated lncRNAs, including both known and novel transcripts, LINC00341 is one of the most abundant lncRNAs in endothelial cells. Moreover, its expression level is enhanced by atheroprotective pulsatile shear flow and atorvastatin. Overexpression of LINC00341 suppresses the expression of vascular cell adhesion molecule 1 (VCAM1) and the adhesion of monocytes induced by atheroprone flow and tumor necrosis factor-alpha. Underlying this anti-inflammatory role, LINC00341 guides enhancer of zest homolog 2, a core histone methyltransferase of polycomb repressive complex 2, to the promoter region of the VCAM1 gene to suppress VCAM1. Network analysis reveals that the key signaling pathways (e.g., Rho and PI3K/AKT) are co-regulated with LINC00341 in endothelial cells in response to pulsatile shear. Together, these findings suggest that LINC00341, as an example of lncRNAs, plays important roles in modulating endothelial function in health and disease.

Proteasome from cytokine-treated human cells shows stimulated BrAAP activity and depressed PGPH activity

2000 ◽  
Vol 78 (2) ◽  
pp. 115-118 ◽  
Author(s):  
Judith E Nelson ◽  
Claudia Altschuller-Felberg ◽  
Anna Loukissa ◽  
Christopher Cardozo
Keyword(s):  
Interferon Gamma ◽  
Umbilical Vein ◽  
Necrosis Factor Alpha ◽  
Multicatalytic Proteinase ◽  
Branched Chain Amino Acid ◽  
Factor Alpha ◽  
Branched Chain ◽  
Umbilical Vein Endothelial Cells ◽  
Multicatalytic Proteinase Complex ◽  
Necrosis Factor

The branched chain amino acid-preferring (BrAAP) activity of multicatalytic proteinase complex isolated from human umbilical vein endothelial cells and treated with interferon-gamma was increased more than 2-fold, which was associated with a marked increase in LMP7 expression and decreased peptidylglutamyl peptide-hydrolyzing activity. Increases in BrAAP activity in supernatants from cells treated with interferon-gamma, tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, or lipopolysaccharide paralleled the increases in LMP7 expression. These findings are consistent with the conclusion that the increased BrAAP activity of LMP-containing multicatalytic proteinase complex results from incorporation of LMP7 or other LMP subunits.

scholarly journals p38 Mitogen-Activated Protein Kinase Mediates Lipopolysaccharide and Tumor Necrosis Factor Alpha Induction of Shiga Toxin 2 Sensitivity in Human Umbilical Vein Endothelial Cells

2007 ◽  
Vol 76 (3) ◽  
pp. 1115-1121 ◽  
Author(s):  
Matthew K. Stone ◽  
Glynis L. Kolling ◽  
Matthew H. Lindner ◽  
Tom G. Obrig
Keyword(s):  
Endothelial Cells ◽  
Intracellular Signaling ◽  
Umbilical Vein ◽  
Mitogen Activated Protein Kinase ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Shiga Toxin 2 ◽  
Factor Alpha ◽  
Umbilical Vein Endothelial Cells

ABSTRACTEscherichia coliO157:H7 Shiga toxin 2 (Stx2), one of the causative agents of hemolytic-uremic syndrome, is toxic to endothelial cells, including primary cultured human umbilical vein endothelial cells (HUVEC). This sensitivity of cells to Stx2 can be increased with either lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNF-α). The goal of the present study was to identify the intracellular signaling pathway(s) by which LPS and TNF-α sensitize HUVEC to the cytotoxic effects of Stx2. To identify these pathways, specific pharmacological inhibitors and small interfering RNAs were tested with cell viability endpoints. A time course and dose response experiment for HUVEC exposure to LPS and TNF-α showed that a relatively short exposure to either agonist was sufficient to sensitize the cells to Stx2 and that both agonists stimulated intracellular signaling pathways within a short time. Cell viability assays indicated that the p38 mitogen-activated protein kinase (MAPK) inhibitors SB202190 and SB203580 and the general protein synthesis inhibitor cycloheximide inhibited both the LPS and TNF-α sensitization of HUVEC to Stx2, while all other inhibitors tested did not inhibit this sensitization. Additionally, SB202190 reduced the cellular globotriaosylceramide content under LPS- and TNF-α-induced conditions. In conclusion, our results show that LPS and TNF-α induction of Stx2 sensitivity in HUVEC is mediated through a pathway that includes p38 MAPK. These results indicate that inhibition of p38 MAPK in endothelial cells may protect a host from the deleterious effects of Stx2.

scholarly journals Carcinoembryonic Antigen Family Receptor Specificity of Neisseria meningitidis Opa Variants Influences Adherence to and Invasion of Proinflammatory Cytokine-Activated Endothelial Cells

2000 ◽  
Vol 68 (6) ◽  
pp. 3601-3607 ◽  
Author(s):  
Petra Muenzner ◽  
Christoph Dehio ◽  
Taku Fujiwara ◽  
Mark Achtman ◽  
Thomas F. Meyer ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Neisseria Meningitidis ◽  
Carcinoembryonic Antigen ◽  
Cell Lines ◽  
Meningococcal Disease ◽  
Proinflammatory Cytokine ◽  
Umbilical Vein ◽  
Necrosis Factor Alpha ◽  
High Concentrations ◽  
Umbilical Vein Endothelial Cells

ABSTRACT The carcinoembryonic antigen (CEA) family member CEACAM1 (previously called biliary glycoprotein or CD66a) was previously shown to function as a receptor that can mediate the binding of Opa protein-expressing Neisseria meningitidis to both neutrophils and epithelial cells. Since neutrophils and polarized epithelia have both been shown to coexpress multiple CEACAM receptors, we have now extended this work to characterize the binding specificity of meningococcal Opa proteins with other CEA family members. To do so, we used recombinant Escherichia coli expressing nine different Opa variants from three meningococcal strains and stably transfected cell lines expressing single members of the CEACAM family. These infection studies demonstrated that seven of the nine Opa variants bound to at least one CEACAM receptor and that binding to each of these receptors is sufficient to trigger the Opa-dependent bacterial uptake by these cell lines. The other two Opa variants do not appear to bind to either CEACAM receptors or heparan sulfate proteoglycan receptors, which are bound by some gonococcal Opa variants, thus implying a novel class of Opa proteins. We have also extended previous studies by demonstrating induction of CEACAM1 expression after stimulation of human umbilical vein endothelial cells with the proinflammatory cytokine tumor necrosis factor alpha, which is present in high concentrations during meningococcal disease. This induced expression of CEACAM1 leads to an increased Opa-dependent bacterial binding and invasion into the primary endothelia, implying that these interactions may play an important role in the pathogenesis of invasive meningococcal disease.

scholarly journals Molecular Targeting of VEGF with a Suramin Fragment–DOCA Conjugate by Mimicking the Action of Low Molecular Weight Heparins

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 46
Author(s):  
Jooho Park ◽  
Tae-Bong Kang ◽  
Ji-Hong Lim ◽  
Hyung-Sik Won
Keyword(s):  
Therapeutic Potential ◽  
Umbilical Vein ◽  
Pharmaceutical Research ◽  
Molecular Targeting ◽  
Drug Candidate ◽  
Heparin Binding ◽  
Vegf Inhibitor ◽  
Acid Conjugate ◽  
Pathogenic Action ◽  
Umbilical Vein Endothelial Cells

Molecular targeting of growth factors has shown great therapeutic potential in pharmaceutical research due to their roles in pathological conditions. In the present study, we developed a novel suramin fragment and deoxycholic acid conjugate (SFD) that exhibited the potential to bind to the heparin-binding site (HBD) of vascular endothelial growth factor (VEGF) and to inhibit its pathogenic action for the first time. Notably, SFD was optimally designed for binding to the HBD of VEGF using the naphthalenetrisulfonate group, allowing to observe its excellent binding efficacy in a surface plasmon resonance (SPR) study, showing remarkable binding affinity (KD = 3.8 nM) as a small molecule inhibitor. In the tubular formation assay, it was observed that SFD could bind to HBD and exhibit antiangiogenic efficacy by inhibiting VEGF, such as heparins. The cellular treatment of SFD resulted in VEGF-inhibitory effects in human umbilical vein endothelial cells (HUVECs). Therefore, we propose that SFD can be employed as a novel drug candidate to inhibit the pathophysiological action of VEGF in diseases. Consequently, SFD, which has a molecular structure optimized for binding to HBD, is put forward as a new chemical VEGF inhibitor.

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