scholarly journals Inhibitory Effects of Polaprezine on the Inflammatory Response toHelicobacter pylori

2002 ◽  
Vol 16 (11) ◽  
pp. 785-789 ◽  
Author(s):  
Osamu Handa ◽  
Norimasa Yoshida ◽  
Yukiko Tanaka ◽  
Miho Ueda ◽  
Takeshi Ishikawa ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Zinc Sulphate ◽  
Water Extract ◽  
Gastric Cancer Cell Line ◽  
Mucosal Inflammation ◽  
Chelate Compound ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Adhesive Interactions ◽  
H Pylori

Helicobacter pylori-infected gastrointestinal mucosa is frequently infiltrated by polymorphonuclear leukocytes (PMN) and monocytes, and these invading cells have been implicated in gastrointestinal mucosal inflammation. To clarify the efficacy of polaprezinc, a chelate compound consisting of zinc and L-carnosine, againstH pylori-induced inflammation including PMN infiltration, the in vitro effects of this drug on interleukin (IL)-8 production by an established gastric cancer cell line (MKN 45 cells) and on PMN-endothelial cell adhesive interactions was investigated. Polaprezinc and zinc sulphate inhibited IL-8 production by MKN 45 cells in response to stimulation withH pyloriwater extract (HPE) in a dose-dependent manner from 10-7M to 10-5M. In addition, the expression of CD11b and CD18 on PMN and PMN-dependent adhesion to endothelial cells elicited by HPE was inhibited by polaprezinc and zinc sulphate in a concentration-dependent manner. L-carnosine did not have any effects on IL-8 production or PMN-endothelial cell interactions. These results suggest that polaprezinc, mainly the zinc component, may inhibitH pylori-induced PMN-mediated gastric inflammation by attenuating CD11b/CD18 expression on PMN and IL-8 production from gastric epithelial cells.

scholarly journals Cytokine Expression and Production by Purified Helicobacter pylori Urease in Human Gastric Epithelial Cells

2000 ◽  
Vol 68 (2) ◽  
pp. 664-671 ◽  
Author(s):  
Toshihito Tanahashi ◽  
Masakazu Kita ◽  
Tadashi Kodama ◽  
Yoshio Yamaoka ◽  
Naoki Sawai ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Epithelial Cells ◽  
Proinflammatory Cytokines ◽  
Gastric Cancer Cell Line ◽  
Mucosal Inflammation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Gastric Epithelial Cells ◽  
Cytokine Induction ◽  
H Pylori ◽  
Stimulation Of

ABSTRACT Cytokines have been proposed to play an important role inHelicobacter pylori-associated gastroduodenal diseases, but the exact mechanism of the cytokine induction remains unclear. H. pylori urease, a major component of the soluble proteins extracted from bacterial cells, is considered to be one of the virulence factors for the inflammation in the gastric mucosa that is produced in H. pylori infection. However, the response of human gastric epithelial cells to the stimulation of urease has not been investigated. In the present study, we used human gastric epithelial cells in a primary culture system and examined whetherH. pylori urease stimulates the gastric epithelial cells to induce proinflammatory cytokines by reverse transcription-PCR and enzyme-linked immunosorbent assay. First, by using peripheral blood mononuclear cells (PBMC) and a gastric cancer cell line (MKN-45 cells), we confirmed the ability of purified H. pylori urease to induce the production of proinflammatory cytokines. Furthermore, we demonstrated that the human gastric epithelial cells produced interleukin-6 (IL-6) and tumor necrosis factor alpha, but not IL-8, following stimulation with purified urease. The patterns of cytokine induction differed among human PBMC, MKN-45 cells, and human gastric epithelial cells. These results suggest that the human gastric epithelial cells contribute to the induction of proinflammatory cytokines by the stimulation of H. pylori urease, indicating that the epithelial cells were involved in the mucosal inflammation that accompanied H. pylori infection.

scholarly journals Dabigatran Abrogates Brain Endothelial Cell Permeability in Response to Thrombin

2015 ◽  
Vol 35 (6) ◽  
pp. 985-992 ◽  
Author(s):  
Brian Thomas Hawkins ◽  
Yu-Huan Gu ◽  
Yoshikane Izawa ◽  
Gregory John del Zoppo
Keyword(s):  
Endothelial Cell ◽  
Intracerebral Hemorrhage ◽  
Glucose Deprivation ◽  
Cell Permeability ◽  
Permeability Barrier ◽  
Dependent Manner ◽  
Thromboembolic Stroke ◽  
Concentration Dependent Manner ◽  
Junction Protein ◽  
Endothelial Cell Permeability

Atrial fibrillation (AF) increases the risk and severity of thromboembolic stroke. Generally, antithrombotic agents increase the hemorrhagic risk of thromboembolic stroke. However, significant reductions in thromboembolism and intracerebral hemorrhage have been shown with the antithrombin dabigatran compared with warfarin. As thrombin has been implicated in microvessel injury during cerebral ischemia, we hypothesized that dabigatran decreases the risk of intracerebral hemorrhage by direct inhibition of the thrombin-mediated increase in cerebral endothelial cell permeability. Primary murine brain endothelial cells (mBECs) were exposed to murine thrombin before measuring permeability to 4-kDa fluorescein isothiocyanate-dextran. Thrombin increased mBEC permeability in a concentration-dependent manner, without significant endothelial cell death. Pretreatment of mBECs with dabigatran completely abrogated the effect of thrombin on permeability. Neither the expressions of the endothelial cell β1-integrins nor the tight junction protein claudin-5 were affected by thrombin exposure. Oxygen-glucose deprivation (OGD) also increased permeability; this effect was abrogated by treatment with dabigatran, as was the additive effect of thrombin and OGD on permeability. Taken together, these results indicate that dabigatran could contribute to a lower risk of intracerebral hemorrhage during embolism-associated ischemia from AF by protection of the microvessel permeability barrier from local thrombin challenge.

scholarly journals Antiplatelet Activity of Acylphloroglucinol Derivatives Isolated from Dryopteris crassirhizoma

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2212 ◽  
Author(s):  
Nam-Hui Yim ◽  
Jung-Jin Lee ◽  
BoHyoung Lee ◽  
Wei Li ◽  
Jin Yeul Ma
Keyword(s):  
Platelet Aggregation ◽  
High Performance ◽  
Clinical Symptoms ◽  
Water Extract ◽  
Initial Response ◽  
Butyl Alcohol ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Antiplatelet Activity ◽  
Concentration Dependent Manner

Platelets are an important component of the initial response to vascular endothelial injury; however, platelet dysfunction induces the acute clinical symptoms of thrombotic disorders, which trigger severe cardiovascular diseases such as myocardial infarction, ischemia, and stroke. In this study, we investigated the Dryopteris crassirhizoma’s antiplatelet activity. A water extract of D. crassirhizoma (WDC) was partitioned into dichloromethane (DCM), ethyl acetate, n-butyl alcohol, and water. Among these four fractions, the DCM fraction potently inhibited the collagen-stimulated platelet aggregation in a concentration-dependent manner. From this fraction, five different acylphloroglucinol compounds and one flavonoid were isolated by activity-guided column chromatography. They were identified by comparing their mass, 1H-, and 13C-NMR spectral data with those reported in the literature. Quantifying the six compounds in WDC and its DCM fraction by high-performance liquid chromatography (HPLC) revealed that butyryl-3-methylphloroglucinol (compound 4) was the most abundant in these samples. Additionally, butyryl-3-methylphloroglucinol showed the strongest inhibitory activity in the collagen- and arachidonic acid (AA)-induced platelet aggregation, with inhibition ratios of 92.36% and 89.51% in the collagen and AA-induced platelet aggregation, respectively, without cytotoxicity. On the active concentrations, butyryl-3-methylphloroglucinol significantly suppressed the convulxin-induced platelet activation. Regarding the structure–activity relationships for the five acylphloroglucinol compounds, our results demonstrated that the functional butanonyl, methoxy, and hydroxy groups in butyryl-3-methylphloroglucinol play important roles in antiplatelet activity. The findings indicate that acylphloroglucinols, including butyryl-3-methylphloroglucinol from D. crassirhizom, possess an antiplatelet activity, supporting the use of this species for antiplatelet remedies.

scholarly journals Serum of coronary atherosclerotic heart disease patients induces oxidative stress injury on endothelial cells

Pteridines ◽  
2018 ◽  
Vol 29 (1) ◽  
pp. 97-103
Author(s):  
Huichao Pan ◽  
Min Zhang
Keyword(s):  
Endothelial Cells ◽  
Heart Disease ◽  
Endothelial Cell ◽  
Umbilical Vein ◽  
Treated Group ◽  
Dependent Manner ◽  
Ros Production ◽  
Concentration Dependent Manner ◽  
Stress Injury ◽  
Huvec Proliferation

AbstractEndothelial cell (EC) dysfunction has a fundamental role in the development of atherosclerosis, which leads to myocardial infarction and stroke. The aim of this study is to investigate the effect of serum from patients with coronary atherosclerotic heart disease (CAD) on endothelial cells and investigate the possible mechanism underlying these effects. Serum from 35 patients with CAD and 35 healthy volunteers was collected. Human umbilical vein endothelial cell (HUVEC) proliferation and apoptosis were assessed by a CCK‑8 assay and a flow cytometry assay, respectively. The synthesis of nitric oxide (NO) and reactive oxygen species (ROS) was measured using the nitrate reduction method and DCFH2-DA staining, respectively. The proliferation of HUVECs was inhibited by treatment with serum from CAD patients (P<0.05). Suppression of HUVEC proliferation by CAD serum occurred in a concentration-dependent manner. The synthesis of NO was also reduced in the CAD serum-treated group. Furthermore, the serum from CAD patients increased both apoptosis and intracellular ROS production in HUVECs. Moreover, treatment with tempol antagonized CAD serum-meditated HUVEC injuries. Taken together, these results suggest that HUVEC injury via CAD serum treatment is mediated by ROS production. Tempol may partly reverse this effect by abolishing HUVEC apoptosis.

scholarly journals Phytochemical Evaluation of Lythrum Salicaria Extracts and Their Effects on Guinea-Pig Ileum

2013 ◽  
Vol 8 (9) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Tímea Bencsik ◽  
Loránd Barthó ◽  
Viktor Sándor ◽  
Nóra Papp ◽  
Rita Benkó ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Guinea Pig ◽  
Ethyl Acetate ◽  
Water Extract ◽  
Lythrum Salicaria ◽  
Dependent Manner ◽  
Guinea Pig Ileum ◽  
Concentration Dependent Manner ◽  
Ethanol In Water

n-Hexane, chloroform, ethyl acetate and 50% ethanol in water extracts prepared from the air-dried flowering parts of Lythrum salicaria L. were tested for in vitro pharmacological properties on Guinea-pig ileum, which is suitable for detecting a whole range of neuronal and smooth muscle effects. UHPLC-MS was used to evaluate polyphenol components of the extracts. In the ileum, the most prominent response (46.4% related to 0.5 μM histamine) of the extracts causing smooth muscle contractions were triggered by the 50% ethanol in water extract in a concentration-dependent manner. Atropine, indomethacin and PPADS plus suramin significantly reduced the contractile response caused by this extract. The strongest inhibition was due to atropine. The results suggest that L. salicaria extracts have a moderate muscarinic receptor agonist effect in Guinea-pig ileum and that prostanoids and purinoceptor mechanisms are involved to some extent. Therefore diluted extracts of L. salicaria p.o. could be used as a mild stimulant of gastrointestinal motility. The 50% ethanol in water extract was rich in polyphenols. n-Hexane, chloroform and ethyl acetate extracts failed to contain catechin, caffeic acid, quercetin-3-D-galactoside and rutin, but they all showed spasmogenic effects, and, therefore we do not think that these compounds could be involved in the spasmogenic activity.

Lymphocytic microparticles inhibit angiogenesis by stimulating oxidative stress and negatively regulating VEGF-induced pathways

2008 ◽  
Vol 294 (2) ◽  
pp. R467-R476 ◽  
Author(s):  
Chun Yang ◽  
Bupe R. Mwaikambo ◽  
Tang Zhu ◽  
Carmen Gagnon ◽  
Josiane Lafleur ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Umbilical Vein ◽  
Ros Generation ◽  
Vegf Receptor ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Endothelial Cell Function

Recent studies have demonstrated that lymphocyte-derived microparticles (LMPs) impair endothelial cell function. However, no data currently exist regarding the contribution of LMPs in the regulation of angiogenesis. In the present study, we investigated the effects of LMPs on angiogenesis in vivo and in vitro and demonstrated that LMPs strongly suppressed aortic ring microvessel sprouting and in vivo corneal neovascularization. In vitro, LMPs considerably diminished human umbilical vein endothelial cell survival and proliferation in a concentration-dependent manner. Mechanistically, the antioxidants U-74389G and U-83836E were partially protective against the antiproliferative effects of LMPs, whereas the NADPH oxidase (NOX) inhibitors apocynin and diphenyleneiodonium significantly abrogated these effects. Moreover, LMPs increased not only the expression of the NOX subunits gp91phox, p22phox, and p47phox, but also the production of ROS and NOX-derived superoxide (O2−). Importantly, LMPs caused a pronounced augmentation in the protein expression of the CD36 antiangiogenic receptor while significantly downregulating the protein levels of VEGF receptor type 2 and its downstream signaling mediator, phosphorylated ERK1/2. In summary, LMPs potently suppress neovascularization in vivo and in vitro by augmenting ROS generation via NOX and interfering with the VEGF signaling pathway.

scholarly journals VE-cadherin and β-catenin binding dynamics during histamine-induced endothelial hyperpermeability

2008 ◽  
Vol 294 (4) ◽  
pp. C977-C984 ◽  
Author(s):  
Mingzhang Guo ◽  
Jerome W. Breslin ◽  
Mack H. Wu ◽  
Cara J. Gottardi ◽  
Sarah Y. Yuan
Keyword(s):  
Endothelial Cell ◽  
Barrier Function ◽  
Umbilical Vein ◽  
Vascular Endothelial Cell ◽  
Endothelial Permeability ◽  
Dependent Manner ◽  
Apparent Permeability ◽  
Concentration Dependent Manner ◽  
Cell Adhesions ◽  
Cell Cell

β-Catenin plays an important role in the regulation of vascular endothelial cell-cell adhesions and barrier function by linking the VE-cadherin junction complex to the cytoskeleton. The purpose of this study was to evaluate the effect of β-catenin and VE-cadherin interactions on endothelial permeability during inflammatory stimulation by histamine. We first assessed the ability of a β-catenin binding polypeptide known as inhibitor of β-catenin and T cell factor (ICAT) to compete β-catenin binding to VE-cadherin in vitro. We then overexpressed recombinant FLAG-ICAT in human umbilical vein endothelial cells (HUVECs) to study its impact on endothelial barrier function controlled by cell-cell adhesions. The binding of β-catenin to VE-cadherin was quantified before and after stimulation with histamine along with measurements of transendothelial electrical resistance (TER) and apparent permeability to albumin ( Pa) under the same conditions. The results showed that ICAT bound to β-catenin and competitively inhibited binding of the VE-cadherin cytoplasmic domain to β-catenin in a concentration-dependent manner. Overexpression of FLAG-ICAT in endothelial cell monolayers did not affect their basal permeability properties, as indicated by unaltered TER and Pa; however, the magnitude and duration of histamine-induced decreases in TER were significantly augmented. Likewise, the increase in Pa in the presence of histamine was exacerbated. Overexpression of FLAG-ICAT also significantly decreased the level of β-catenin-associated VE-cadherin following histamine stimulation. Taken together, these data suggest that inflammatory agents like histamine cause a transient and reversible disruption of binding between β-catenin and VE-cadherin, during which endothelial permeability is elevated.

Heterophilic and Homophilic Interactions of Junctional Adhesion Molecule-C (JAM-C) Mediate Different Intercellular Adhesive Interactions.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 534-534
Author(s):  
Triantafyllos Chavakis ◽  
Valeria Orlova ◽  
Kaimei Song ◽  
Cornelia L. Andrei-Selmer ◽  
Sentot Santoso
Keyword(s):  
Endothelial Cell ◽  
Tumor Cell ◽  
Cho Cells ◽  
Cell Interactions ◽  
Single Amino Acid ◽  
Dependent Manner ◽  
Amino Terminal ◽  
Homophilic Interaction ◽  
Adhesive Interactions ◽  
Ig Domain

Abstract Junctional adhesion molecules (JAM) are a new subfamily of the Ig superfamily. We recently identified that the third member of this family, JAM-C, expressed on endothelial, epithelial cells and platelets (i) undergoes a heterophilic interaction with leukocyte β2-integrin Mac-1 (CD11b/CD18) (J Exp Med. 2002; 196:679–91) and (ii) that endothelial JAM-C is predominantly localized within tight junctions and mediates neutrophil transendothelial migration in a Mac-1-dependent manner in vitro and in vivo (J Biol Chem. 2004, 279:55602–8). Here, we characterized JAM-C to undergo a homophilic interaction that participates in tumor cell-endothelial cell interactions. As assessed in a purified system, recombinant soluble JAM-C in fluid phase bound to immobilized JAM-C; moreover, JAM-C-transfected CHO cells adhered to immobilized JAM-C. The homophilic interaction of JAM-C was mediated by the isolated amino-terminal Ig-domain (D1) but not the carboxy-terminal Ig-domain (D2) of the molecule. Dimerization of JAM-A is dependent on the sequence RVE in the aminoterminal Ig-domain. This motif is conserved in JAM-C (R64I65E66) and a single amino acid mutation in this motif (E66R) abolished the homophilic interaction of JAM-C. The lung carcinoma cell line NCI-H522 was found to be positive for JAM-C expression. NCI-H522 cells adhered to immobilized JAM-C, as well as to JAM-C-transfected CHO cells, but not to mock-transfected CHO cells or to CHO cells transfected with the JAM-C mutant (E66R). Adhesion of NCI-H522 cells to JAM-C protein or JAM-C-transfected CHO cells was abolished in the presence of soluble JAM-C or the isolated D1. Furthermore, the adhesion of NCI-H522 cells to endothelial cells was significantly blocked by soluble JAM-C or the isolated D1. Thus, JAM-C undergoes a homophilic interaction via the R64I65E66 motif on the membrane-distal Ig-domain of the molecule. The homophilic interaction of JAM-C can mediate tumor cell-endothelial cell interactions and may thereby be involved in the process of tumor cell metastasis. Together, the heterophilic and homophilic interactions of JAM-C mediate distinct adhesive interactions.

Comparison of the Effects of Heparin and Hirudin on Thrombin Binding to the Normal and the De-Endothelialized Rabbit Aorta In Vitro

1991 ◽  
Vol 66 (02) ◽  
pp. 208-212 ◽  
Author(s):  
Mark W C Hatton ◽  
Susan L Moar
Keyword(s):  
Endothelial Cell ◽  
Cell Membrane ◽  
Binding Site ◽  
Antithrombin Iii ◽  
Rabbit Aorta ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Separate Site ◽  
Protease Nexin

SummaryThe properties of heparin and hirudin to inhibit thrombin from binding to the freshly-excised rabbit aorta wall were compared in vitro. When aorta segments were incubated with 125I-thrombin (4.4 ± 0.4 nM) in the presence of heparin or hirudin, both anticoagulants inhibited 125I-thrombin binding to the endothelium in a concentration-dependent manner (IC50: 0.1 USP U heparin/ml; 0.1 ATU hirudin/ml). Endothelium-bound 125I-thrombin was displaced by either heparin (50% liberated at 4.1 U/ml) or hirudin (0.4 U/ml). Using de-endothelialized aortas, heparin inhibited thrombin binding by the exposed subendothelium (IC50: 1.8 U/ml) whereas hirudin was without effect. Neither heparin nor hirudin was able to significantly liberate thrombin bound to the exposed subendothelium. These observations suggest that both heparin and hirudin mask the binding site on thrombin to the endothelial cell membrane. A separate site on thrombin must bind to the subendothelium because only heparin inhibits binding. Thrombin, although bound reversibly to the endothelium, is bound irreversibly to the exposed subendothelium due, probably, to reaction with endogenous extracellular antithrombin activities (e.g. antithrombin-III, protease nexin-1).

scholarly journals In vitro Antibacterial Activity of Zingiber officinale and Orthosiphon stamineus on Enterococcus faecalis

2017 ◽  
Vol 9 (13) ◽  
pp. 112 ◽  
Author(s):  
Zamirah Zainal-Abidin ◽  
Nor Akmal Abdul-Wahab ◽  
Muhamad Kamil Ghazi-Ahmad ◽  
Shahida Mohd-Said
Keyword(s):  
Antibacterial Activity ◽  
Enterococcus Faecalis ◽  
Water Extract ◽  
Zingiber Officinale ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Orthosiphon Stamineus ◽  
Biofilm Disruption

This study evaluates the antibacterial effects of Zingiber officinale essential oil and Orthosiphon stamineus water extract against Enterococcus faecalis. The herbs were prepared in various concentrations to determine their minimum inhibitory concentrations (MIC) and growth inhibitory effect. Anti-adhesion activities of the herbs were determined by co-incubation with E. faecalis cultures for 6 and 24 h. Biofilm disruption activities were determined by adding the studied herbs into preformed E. faecalis biofilm. The effects on the morphology of E. faecalis grown as biofilm were studied using scanning electron microscopy (SEM). The MICs of ginger oil and O. stamineus extract were 0.31 and 25 mg/mL, respectively. Between the tested herbs, ginger exhibited greater inhibitory effects on the growth of E. faecalis grown in suspension mode. Both herbs generally showed anti-adhesion activities in inverse concentration-dependent manner. No significant biofilm disruption activities by both herbs were observed. SEM analyses showed E. faecalis cell surface changes in the treated biofilm. The studied herbs may have compromised the integrity of the bacterial cell membrane. These findings suggest that the studied herbs may have better antibacterial activities against E. faecalis in suspension mode compared to biofilm mode, with ginger oil showed greater antibacterial activity compared to O. stamineus extract.

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