scholarly journals Zc3h12c inhibits vascular inflammation by repressing NF-κB activation and pro-inflammatory gene expression in endothelial cells

2013 ◽  
Vol 451 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Ling Liu ◽  
Zhou Zhou ◽  
Shengping Huang ◽  
Yanhong Guo ◽  
Yanbo Fan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Zinc Finger ◽  
Nuclear Translocation ◽  
Inflammatory Diseases ◽  
Umbilical Vein ◽  
Vascular Inflammation ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Induced Expression ◽  
Adhesive Molecules

Endothelial activation characterized by the expression of multiple chemokines and adhesive molecules is a critical initial step of vascular inflammation, which results in recruitment of leucocytes into the sub-endothelial layer of the vascular wall and triggers vascular inflammatory diseases such as atherosclerosis. Although inhibiting endothelial inflammation has already been well recognized as a therapeutic strategy in vascular inflammatory diseases, the therapeutic targets are still elusive. In the present study we found that Zc3h12c (zinc finger CCCH-type-containing 12C), a recently discovered CCCH zinc finger-containing protein, significantly inhibited the endothelial cell inflammatory response in vitro. Overexpression of Zc3h12c significantly attenuated TNFα (tumour necrosis factor α)-induced expression of chemokines and adhesive molecules, and thus reduced monocyte adherence to HUVECs (human umbilical vein endothelial cells). Conversely, siRNA (small interfering RNA)-mediated knockdown of Zc3h12c increased the TNFα-induced expression of chemokines and adhesive molecules in HUVECs. Furthermore, forced expression of Zc3h12c decreased TNFα-induced IKKα/β [IκB (inhibitor of nuclear factor κB) kinase α/β], IκBα phosphorylation and p65 nuclear translocation, suggesting that Zc3h12c exerted its anti-inflammatory function probably by suppressing the NF-κB (nuclear factor κB) pathway. Thus Zc3h12c is an endogenous inhibitor of TNFα-induced inflammatory signalling in HUVECs and might be a therapeutic target in vascular inflammatory diseases.

scholarly journals Thrombin Stimulation of the Vascular Cell Adhesion Molecule-1 Promoter in Endothelial Cells Is Mediated by Tandem Nuclear Factor-κB and GATA Motifs

2001 ◽  
Vol 276 (50) ◽  
pp. 47632-47641 ◽  
Author(s):  
Takashi Minami ◽  
William C. Aird
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Umbilical Vein ◽  
Fold Increase ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Mobility Shift ◽  
Response Element ◽  
Vascular Adhesion ◽  
Stimulation Of

The goal of this study was to delineate the transcriptional mechanisms underlying thrombin-mediated induction of vascular adhesion molecule-1 (VCAM-1). Treatment of human umbilical vein endothelial cells with thrombin resulted in a 3.3-fold increase in VCAM-1 promoter activity. The upstream promoter region of VCAM-1 contains a thrombin response element, two nuclear factor κB (NF-κB) motifs, and a tandem GATA motif. In transient transfection assays, mutation of the thrombin response element had no effect on thrombin induction. In contrast, mutation of either NF-κB site resulted in a complete loss of induction, whereas a mutation of the two GATA motifs resulted in a significant reduction in thrombin stimulation. In electrophoretic mobility shift assays, nuclear extracts from thrombin-treated endothelial cells displayed markedly increased binding to the tandem NF-κB and GATA motifs. The NF-κB complex was supershifted with anti-p65 antibodies, but not with antibodies to RelB, c-Rel, p50, or p52. The GATA complex was supershifted with antibodies to GATA-2, but not GATA-3 or GATA-6. A construct containing tandem copies of the VCAM-1 GATA motifs linked to a minimal thymidine kinase promoter was induced 2.4-fold by thrombin. Taken together, these results suggest that thrombin stimulation of VCAM-1 in endothelial cells is mediated by the coordinate action of NF-κB and GATA transcription factors.

scholarly journals Sodium tanshinone IIA sulfonate prevents lipopolysaccharide-induced inflammation via suppressing nuclear factor-κB signaling pathway in human umbilical vein endothelial cells

2018 ◽  
Vol 96 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Jun Cheng ◽  
Tangting Chen ◽  
Pengyun Li ◽  
Jing Wen ◽  
Ningbo Pang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
Umbilical Vein ◽  
Nuclear Factor Κb ◽  
Tanshinone Iia ◽  
Nuclear Factor ◽  
Human Umbilical Vein ◽  
Tnf Α ◽  
Sodium Tanshinone Iia Sulfonate ◽  
Umbilical Vein Endothelial Cells

Sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, has been demonstrated to have potent anti-inflammatory properties. However, the protective effects of STS on lipopolysaccharide (LPS)-induced inflammation in endothelial cells remain to be elucidated. In the present study, human umbilical vein endothelial cells (HUVECs) were used to explore the effects of STS on LPS-induced inflammation and the molecular mechanism involved. HUVECs were pretreated with STS for 2 h, followed by stimulation with LPS. Then expression and secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and the activation of nuclear factor-κB (NF-κB) were assessed. The results demonstrated that STS significantly decreased LPS-induced TNF-α and IL-1β protein expression in HUVECs. Similarly, the increased levels of TNF-α and IL-1β in cell supernatants stimulated by LPS were also significantly inhibited by STS. Furthermore, STS inhibited LPS-induced NF-κB p65 phosphorylation and nuclear translocation. All the results suggest that STS prevents LPS-induced inflammation through suppressing NF-κB signaling pathway in endothelial cells, indicating the potential utility of STS for the treatment of inflammatory diseases.

scholarly journals Transcription of the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase type 3 gene, ATP2A3, is regulated by the calcineurin/NFAT pathway in endothelial cells

2006 ◽  
Vol 394 (1) ◽  
pp. 27-33 ◽  
Author(s):  
Lahouaria Hadri ◽  
Catherine Pavoine ◽  
Larissa Lipskaia ◽  
Sabrina Yacoubi ◽  
Anne-Marie Lompré
Keyword(s):  
Endothelial Cells ◽  
Endoplasmic Reticulum ◽  
Nuclear Translocation ◽  
Umbilical Vein ◽  
Nuclear Factor ◽  
H1 Receptor ◽  
Activated T Cells ◽  
Cycling Treatment ◽  
Ea.Hy926 Cells ◽  
Type 3

Histamine, known to induce Ca2+ oscillations in endothelial cells, was used to alter Ca2+ cycling. Treatment of HUVEC (human umbilical-vein endothelial cell)-derived EA.hy926 cells with histamine for 1–3 days increased the levels of SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) 3, but not of SERCA 2b, transcripts and proteins. Promoter-reporter gene assays demonstrated that this increase in expression was due to activation of SERCA 3 gene transcription. The effect of histamine was abolished by mepyramine, but not by cimetidine, indicating that the H1 receptor, but not the H2 receptor, was involved. The histamine-induced up-regulation of SERCA 3 was abolished by cyclosporin A and by VIVIT, a peptide that prevents calcineurin and NFAT (nuclear factor of activated T-cells) from interacting, indicating involvement of the calcineurin/NFAT pathway. Histamine also induced the nuclear translocation of NFAT. NFAT did not directly bind to the SERCA 3 promoter, but activated Ets-1 (E twenty-six-1), which drives the expression of the SERCA 3 gene. Finally, cells treated with histamine and loaded with fura 2 exhibited an improved capacity in eliminating high cytosolic Ca2+ concentrations, in accordance with an increase in activity of a low-affinity Ca2+-ATPase, like SERCA 3. Thus chronic treatment of endothelial cells with histamine up-regulates SERCA 3 transcription. The effect of histamine is mediated by the H1R (histamine 1 receptor) and involves activation of the calcineurin/NFAT pathway. By increasing the rate of Ca2+ sequestration, up-regulation of SERCA 3 counteracts the cytosolic increase in Ca2+ concentration.

scholarly journals Activation of nuclear factor-κB during doxorubicin-induced apoptosis in endothelial cells and myocytes is pro-apoptotic: the role of hydrogen peroxide

2002 ◽  
Vol 367 (3) ◽  
pp. 729-740 ◽  
Author(s):  
Suwei WANG ◽  
Srigiridhar KOTAMRAJU ◽  
Eugene KONOREV ◽  
Shasi KALIVENDI ◽  
Joy JOSEPH ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Nuclear Translocation ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Apoptotic Pathway ◽  
Toxic Side Effect ◽  
Rat Cardiomyocytes ◽  
A Cell ◽  
Induced Apoptosis

Doxorubicin (DOX) is a widely used anti-tumour drug. Cardiotoxicity is a major toxic side effect of DOX therapy. Although recent studies implicated an apoptotic pathway in DOX-induced cardiotoxicity, the mechanism of DOX-induced apoptosis remains unclear. In the present study, we investigated the role of reactive oxygen species and the nuclear transcription factor nuclear factor κB (NF-κB) during apoptosis induced by DOX in bovine aortic endothelial cells (BAECs) and adult rat cardiomyocytes. DOX-induced NF-κB activation is both dose- and time-dependent, as demonstrated using electrophoretic mobility-shift assay and luciferase and p65 (Rel A) nuclear-translocation assays. Addition of a cell-permeant iron metalloporphyrin significantly suppressed NF-κB activation and apoptosis induced by DOX. Overexpression of glutathione peroxidase, which detoxifies cellular H2O2, significantly decreased DOX-induced NF-κB activation and apoptosis. Inhibition of DOX-induced NF-κB activation by a cell-permeant peptide SN50 that blocks translocation of the NF-κB complex into the nucleus greatly diminished DOX-induced apoptosis. Apoptosis was inhibited when IκB mutant vector, another NF-κB inhibitor, was added to DOX-treated BAECs. These results suggest that NF-κB activation in DOX-treated endothelial cells and myocytes is pro-apoptotic, in contrast with DOX-treated cancer cells, where NF-κB activation is anti-apoptotic. Removal of intracellular H2O2 protects endothelial cells and myocytes from DOX-induced apoptosis, possibly by inhibiting NF-κB activation. These findings suggest a novel mechanism for enhancing the therapeutic efficacy of DOX.

scholarly journals Cyclolinteinone, a sesterterpene from sponge Cacospongia linteiformis, prevents inducible nitric oxide synthase and inducible cyclo-oxygenase protein expression by blocking nuclear factor-κB activation in J774 macrophages

2000 ◽  
Vol 346 (3) ◽  
pp. 793-798 ◽  
Author(s):  
Fulvio D'ACQUISTO ◽  
Virginia LANZOTTI ◽  
Rosa CARNUCCIO
Keyword(s):  
Nitric Oxide ◽  
Protein Expression ◽  
Nuclear Translocation ◽  
Inflammatory Diseases ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Mobility Shift ◽  
J774 Cells ◽  
Cox 2 ◽  
Mobility Shift Assay

We investigated the effect of cyclolinteinone, a sesterterpene from Caribbean sponge Cacospongia linteiformis, on inducible NO synthase (iNOS) and cyclo-oxygenase-2 (COX-2) protein expression in lipopolysaccharide (LPS)-stimulated J774 macrophages. Incubation of J774 cells with LPS (1 μg/ml) caused an increase of both iNOS and COX-2 protein expression, which was prevented in a concentration-dependent fashion by cyclolinteinone (12.5, 25 and 50 μM). Electrophoretic mobility-shift assay indicated that cyclolinteinone blocked the activation of nuclear factor-ĸB (NF-ĸB), a transcription factor necessary for either iNOS or COX-2 induction. Cyclolinteinone also blocked disappearance of IĸB-α from cytosolic fraction and nuclear translocation of NF-ĸB subunits p50 and p65. These results show that cyclolinteinone down-regulates iNOS and COX-2 protein expression by inhibiting NF-ĸB activation and suggest that it may represent a novel anti-inflammatory compound capable of controlling the excessive production of prostaglandins and nitric oxide occurring in several inflammatory diseases.

scholarly journals Proteasome-Independent Activation of Nuclear Factor κB in Cytoplasmic Extracts from Human Endothelial Cells byRickettsia rickettsii

1998 ◽  
Vol 66 (5) ◽  
pp. 1827-1833 ◽  
Author(s):  
Sanjeev K. Sahni ◽  
Daniel J. Van Antwerp ◽  
Marina E. Eremeeva ◽  
David J. Silverman ◽  
Victor J. Marder ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Umbilical Vein ◽  
Spotted Fever ◽  
Nuclear Factor Κb ◽  
Host Cells ◽  
Nuclear Factor ◽  
Rocky Mountain Spotted Fever ◽  
Free System

ABSTRACT Interaction of many infectious agents with eukaryotic host cells is known to cause activation of the ubiquitous transcription factor nuclear factor κB (NF-κB) (U. Siebenlist, G. Franzoso, and K. Brown, Annu. Rev. Cell Biol. 10:405–455, 1994). Recently, we reported a biphasic pattern of NF-κB activation in cultured human umbilical vein endothelial cells consequent to infection withRickettsia rickettsii, an obligate intracellular gram-negative bacterium and the etiologic agent of Rocky Mountain spotted fever (L. A. Sporn, S. K. Sahni, N. B. Lerner, V. J. Marder, D. J. Silverman, L. C. Turpin, and A. L. Schwab, Infect. Immun. 65:2786–2791, 1997). In the present study, we describe activation of NF-κB in a cell-free system, accomplished by addition of partially purified R. rickettsii to endothelial cell cytoplasmic extracts. This activation was rapid, reaching maximal levels at 60 min, and was dependent on the number ofR. rickettsii organisms added. Antibody supershift assays using monospecific antisera against NF-κB subunits (p50 and p65) confirmed the authenticity of the gel-shifted complexes and identified both p50-p50 homodimers and p50-p65 heterodimers as constituents of the activated NF-κB pool. Activation occurred independently of the presence of endothelial cell membranes and was not inhibited by removal of the endothelial cell proteasome. Lack of involvement of the proteasome was further confirmed in assays using the peptide-aldehyde proteasome inhibitor MG 132. Activation was not ATP dependent since no change in activation resulted from addition of an excess of the unhydrolyzable ATP analog ATPγS, supplementation with exogenous ATP, or hydrolysis of endogenous ATP with ATPase. Furthermore, Western blot analysis before and after in vitro activation failed to demonstrate phosphorylation of serine 32 or degradation of the cytoplasmic pool of IκBα. This lack of IκBα involvement was supported by the finding that R. rickettsii can induce NF-κB activation in cytoplasmic extracts prepared from T24 bladder carcinoma cells and human embryo fibroblasts stably transfected with a superrepressor phosphorylation mutant of IκBα, rendering NF-κB inactivatable by many known signals. Thus, evidence is provided for a potentially novel NF-κB activation pathway wherein R. rickettsii may interact with and activate host cell transcriptional machinery independently of the involvement of the proteasome or known signal transduction pathways.

HMGB1 activates nuclear factor-κB signaling by RAGE and increases the production of TNF-α in human umbilical vein endothelial cells

Immunobiology ◽  
2010 ◽  
Vol 215 (12) ◽  
pp. 956-962 ◽  
Author(s):  
Zheng-Gang Luan ◽  
Hao Zhang ◽  
Ping-Ting Yang ◽  
Xiao-Chun Ma ◽  
Cheng Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Human Umbilical Vein ◽  
Tnf Α ◽  
Umbilical Vein Endothelial Cells

Ketamine attenuates high-glucose-mediated endothelial inflammation in human umbilical vein endothelial cells

2020 ◽  
Vol 98 (3) ◽  
pp. 156-161
Author(s):  
Tianhai Wang ◽  
Hongge Zhu ◽  
Yanshen Hou ◽  
Wenming Duan ◽  
Fufen Meng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Adhesion Molecule ◽  
High Glucose ◽  
Nuclear Translocation ◽  
Umbilical Vein ◽  
Nuclear Factor ◽  
Adhesion Molecule Expression ◽  
Endothelial Adhesion Molecule ◽  
Umbilical Vein Endothelial Cells

Hyperglycemia mediates oxidative stress, thus inducing transcription factor nuclear factor kappa B (NF-κB) activation, increasing endothelial adhesion molecule expression and monocyte/endothelial interaction, and resulting in endothelial injury. Ketamine was reported to attenuate oxidative stress in many cases. In this research, we determined whether and how ketamine protects against high-glucose-mediated augmentation of monocyte/endothelial interaction and endothelial adhesion molecule expression in human umbilical vein endothelial cells. High glucose augmented monocyte/endothelial adhesion and endothelial adhesion molecule expression. High glucose induced reactive oxygen species (ROS) production and augmented phospho-protein kinase C (p-PKC) βII expression and PKC activity. Moreover, high glucose inhibited the inhibitory subunit of nuclear factor-κBα (IκBα) expression in the cytoplasm and induced NF-κB nuclear translocation. Importantly, the effects induced by high glucose were counteracted by ketamine treatment. Further, CGP53353, a PKC βII inhibitor, inhibited high-glucose-mediated NF-κB nuclear translocation, attenuated adhesion molecule expression, and reduced monocyte/endothelial interaction. Further, these effects of ketamine against high-glucose-induced endothelial injury were inhibited by phorbol 12-myristate 13-acetate, a PKC βII activator. In conclusion, ketamine, via reducing ROS accumulation, inhibited PKC βII Ser660 phosphorylation and PKC and NF-κB activation and reduced high-glucose-induced expression of endothelial adhesion molecules and monocyte/endothelial interaction.

Sign in / Sign up

Export Citation Format

Share Document