scholarly journals Histamine induces interleukin-8 secretion by endothelial cells

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2229-2233 ◽  
Author(s):  
P Jeannin ◽  
Y Delneste ◽  
P Gosset ◽  
S Molet ◽  
P Lassalle ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Platelet Activating Factor ◽  
Surface Expression ◽  
Histamine Receptor ◽  
Leukotriene B4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Delayed Effects ◽  
Allergic Disorders ◽  
Dose Dependent

It has been shown that histamine induces early changes on endothelial cells (EC), such as a transient expression of P-selectin and secretion and/or surface expression of early mediators (eg, prostacyclin [PG1(2)], platelet-activating factor [PAF], and leukotriene B4 [LTB4]). However, delayed effects of histamine on EC and particularly on cytokine production are undefined. In this study, the effect of histamine on interleukin (IL)-8 production by EC was evaluated using an enzyme-linked immunosorbent assay (ELISA) method and mRNA expression. The results showed that histamine increased the secretion and the mRNA expression of IL-8 by EC. Histamine-induced IL-8 production was (1) dose-dependent (at a dose > or = 10(-6) mol/L), (2) potentialized by costimulation with tumor necrosis factor (TNF)-alpha, (3) inhibited by H1 or H2 histamine receptor antagonists, and (4) significantly increased 4 hours after the initial stimulation. These data suggest that histamine may be involved in the control of the late inflammatory reaction associated to allergic disorders through IL-8 secretion by EC.

scholarly journals Histamine induces interleukin-8 secretion by endothelial cells

Blood ◽  
1994 ◽  
Vol 84 (7) ◽  
pp. 2229-2233 ◽  
Author(s):  
P Jeannin ◽  
Y Delneste ◽  
P Gosset ◽  
S Molet ◽  
P Lassalle ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Platelet Activating Factor ◽  
Surface Expression ◽  
Histamine Receptor ◽  
Leukotriene B4 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Delayed Effects ◽  
Allergic Disorders ◽  
Dose Dependent

Abstract It has been shown that histamine induces early changes on endothelial cells (EC), such as a transient expression of P-selectin and secretion and/or surface expression of early mediators (eg, prostacyclin [PG1(2)], platelet-activating factor [PAF], and leukotriene B4 [LTB4]). However, delayed effects of histamine on EC and particularly on cytokine production are undefined. In this study, the effect of histamine on interleukin (IL)-8 production by EC was evaluated using an enzyme-linked immunosorbent assay (ELISA) method and mRNA expression. The results showed that histamine increased the secretion and the mRNA expression of IL-8 by EC. Histamine-induced IL-8 production was (1) dose-dependent (at a dose > or = 10(-6) mol/L), (2) potentialized by costimulation with tumor necrosis factor (TNF)-alpha, (3) inhibited by H1 or H2 histamine receptor antagonists, and (4) significantly increased 4 hours after the initial stimulation. These data suggest that histamine may be involved in the control of the late inflammatory reaction associated to allergic disorders through IL-8 secretion by EC.

Inhibition of neutrophil L-selectin shedding: a potential anti-inflammatory effect of aprotinin

Perfusion ◽  
2000 ◽  
Vol 15 (6) ◽  
pp. 495-499 ◽  
Author(s):  
George Asimakopoulos ◽  
Kenneth M Taylor ◽  
Dorian O Haskard ◽  
R Clive Landis
Keyword(s):  
Endothelial Cell ◽  
Venous Blood ◽  
Platelet Activating Factor ◽  
Surface Expression ◽  
Cell Interaction ◽  
Dose Dependent Fashion ◽  
Anti Inflammatory ◽  
Dose Dependent ◽  
Inflammatory Action ◽  
Inflammatory Effect

The cardiopulmonary bypass (CPB)-related inflammatory response involves leucocyte activation and increased leucocyte-endothelial cell interaction. L-selectin is an adhesion molecule expressed on the surface of leucocytes which participates in the initial rolling step of the leucocyte-endothelial cell adhesion cascade. L-selectin is proteolytically cleaved off the surface of leucocytes when they become activated, an event that is regarded as a marker of leucocyte activation. Aprotinin is a protease inhibitor that has been used in cardiac surgery as a haemostatic agent and also exhibits certain anti-inflammatory properties. In this study, peripheral venous blood from volunteers was pre-incubated with aprotinin at 200, 800 and 1600 kallikrein inhibiting units (kiu)/ml and stimulated with the chemoattractants N-formyl-methyl-leucyl-phenylalanine (fMLP) or platelet activating factor (PAF). Surface expression of L-selectin on neutrophils was measured using a monoclonal antibody and flow cytometry. The results demonstrate that aprotinin inhibits shedding of L-selectin in a dose-dependent fashion ( p=0.0278 and 0.0005, respectively, at 800 and 1600 kiu/ml for fMLP-stimulated shedding; p=0.0017 and 0.0010, respectively, at 200 and 800 kiu/ml for PAF-stimulated shedding). This effect may be of significance with respect to the anti-inflammatory action of aprotinin in patients undergoing CPB.

scholarly journals GAS6 Inhibits Granulocyte Adhesion to Endothelial Cells

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2334-2340
Author(s):  
Gian Carlo Avanzi ◽  
Margherita Gallicchio ◽  
Flavia Bottarel ◽  
Loretta Gammaitoni ◽  
Giuliana Cavalloni ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Platelet Activating Factor ◽  
Polymorphonuclear Cells ◽  
Vascular Endothelial ◽  
Tnf Α ◽  
High Concentrations ◽  
Adhesive Interactions ◽  
Factor Α ◽  
Dose Dependent

GAS6 is a ligand for the tyrosine kinase receptors Rse, Axl, and Mer, but its function is poorly understood. Previous studies reported that both GAS6 and Axl are expressed by vascular endothelial cells (EC), which play a key role in leukocyte extravasation into tissues during inflammation through adhesive interactions with these cells. The aim of this work was to evaluate the GAS6 effect on the adhesive function of EC. Treatment of EC with GAS6 significantly inhibited adhesion of polymorphonuclear cells (PMN) induced by phorbol 12-myristate 13-acetate (PMA), platelet-activating factor (PAF), thrombin, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), but not that induced by FMLP and IL-8. GAS6 did not affect adhesion to resting EC. Titration experiments showed that high concentrations of GAS6 were needed to inhibit PMN adhesion and that inhibition was dose-dependent at the concentration range of 0.1 to 1 μg/mL. One possibility was that high concentrations were needed to overwhelm the effect of endogenous GAS6 produced by EC. In line with this possibility, treatment of resting EC with soluble Axl significantly potentiated PMN adhesion. Analysis of localization of GAS6 by confocal microscopy and cytofluorimetric analysis showed that it is concentrated along the plasma membrane in resting EC and treatment with PAF induces depletion and/or redistribution of the molecule. These data suggest that GAS6 functions as a physiologic antiinflammatory agent produced by resting EC and depleted when proinflammatory stimuli turn on the proadhesive machinery of EC.

scholarly journals Wegener's Granulomatosis: Anti–proteinase 3 Antibodies Are Potent Inductors of Human Endothelial Cell Signaling and Leakage Response

1998 ◽  
Vol 187 (4) ◽  
pp. 497-503 ◽  
Author(s):  
Ulf Sibelius ◽  
Katja Hattar ◽  
Angelika Schenkel ◽  
Thomas Noll ◽  
Elena Csernok ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Wegener’S Granulomatosis ◽  
Inositol Phosphates ◽  
Vascular Endothelial Cells ◽  
Platelet Activating Factor ◽  
Barrier Properties ◽  
Wegener's Granulomatosis ◽  
Phosphoinositide Hydrolysis ◽  
Proteinase 3 ◽  
Dose Dependent

Anti–neutrophil cytoplasmic antibodies (ANCAs) targeting proteinase 3 (PR3) have a high specifity for Wegener's granulomatosis (WG), and their role in activating leukocytes is well appreciated. In this study, we investigated the influence of PR3-ANCA and murine monoclonal antibodies on human umbilical vascular endothelial cells (HUVECs). Priming of HUVECs with tumor necrosis factor α induced endothelial upregulation of PR3 message and surface expression of this antigen, as measured by Cyto-ELISA, with a maximum occurrence after 2 h. Primed cells responded to low concentrations of both antibodies (25 ng–2.5 μg/ml), but not to control immunoglobulins, with pronounced, dose-dependent phosphoinositide hydrolysis, as assessed by accumulation of inositol phosphates. The signaling response peaked after 20 min, in parallel with the appearance of marked prostacyclin and platelet-activating factor synthesis. The F(ab)2 fragment of ANCA was equally potent as ANCA itself. Disrupture of the endothelial F-actin content by botulinum C2 toxin to avoid antigen–antibody internalization did not affect the response. In addition to the metabolic events, anti-PR3 challenge, in the absence of plasma components, provoked delayed, dose-dependent increase in transendothelial protein leakage. We conclude that anti-PR3 antibodies are potent inductors of the preformed phosphoinositide hydrolysis–related signal tranduction pathway in human endothelial cells. Associated metabolic events and the loss of endothelial barrier properties suggest that anti-PR3–induced activation of endothelial cells may contribute to the pathogenetic sequelae of autoimmune vasculitis characterizing WG.

Atorvastatin suppresses LPS-induced rapid upregulation of Toll-like receptor 4 and its signaling pathway in endothelial cells

2011 ◽  
Vol 300 (5) ◽  
pp. H1743-H1752 ◽  
Author(s):  
Ying Wang ◽  
Ming Xiang Zhang ◽  
Xiao Meng ◽  
Fu Qiang Liu ◽  
Guang Sheng Yu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Umbilical Vein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Mapk Phosphorylation ◽  
Tlr4 Mrna

In the present study, we tested our hypothesis that atorvastatin exerts its anti-inflammation effect via suppressing LPS-induced rapid upregulation of Toll-like receptor 4 (TLR4) mRNA and its downstream p38, ERK, and NF-κB signaling pathways in human umbilical-vein endothelial cells (HUVECs) and human aortic endothelial cells (HAECs). TLR4 mRNA expression and its downstream kinase activities induced by LPS alone or atorvastatin + LPS in endothelial cells were quantified using quantitative real-time PCR and enzyme-linked immunosorbent assay. Preincubation of LPS-stimulated endothelial cells with TLR4 siRNA was conducted to identify the target of the anti-inflammatory effects of atorvastatin. Atorvastatin incubation resulted in the reduction of LPS-induced TLR4 mRNA expression, ERK1/2 and P38 MAPK phosphorylation, and NF-κB binding activity. Pretreatment with MEK/ERK1/2 inhibitor PD98059 attenuated atorvastatin + LPS-induced NF-κB activity but had no effect on P38 MAPK phosphorylation. In contrast, pretreatment with P38 MAPK inhibitor SB203580 resulted in upregulation of atorvastatin + LPS-induced ERK1/2 phosphorylation but had no significant effects on NF-κB activity. On the other hand, blocking NF-κB with SN50 produced no effects on atorvastatin + LPS-induced ERK1/2 and P38 MAPK phosphorylation. Moreover, TLR4 gene silencing produced the same effects as the atorvastatin treatment. In conclusion, atorvastatin downregulated TLR4 mRNA expression by two distinct signaling pathways. First, atorvastatin stabilized Iκ-Bα, which directly inhibited NF-κB activation. Second, atorvastatin inactivated ERK phosphorylation, which indirectly inhibited NF-κB activation. Suppression of p38 MAPK by atorvastatin upregulates ERK but exerts no effect on NF-κB.

scholarly journals Dietary chitosan affects metabolism of arachidonic acid in weaned piglets

2017 ◽  
Vol 62 (No. 2) ◽  
pp. 58-66 ◽  
Author(s):  
J.-L. Li ◽  
Y.-Q. Xu ◽  
B.-L. Shi ◽  
D.-S. Sun ◽  
S.-M. Yan ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Small Intestine ◽  
Immune Function ◽  
Mrna Expression ◽  
Basal Diet ◽  
Leukotriene B4 ◽  
Dependent Manner ◽  
Weaned Piglets ◽  
Cox 2 ◽  
Dose Dependent

The effects of chitosan on immune function via arachidonic acid (AA) pathway in weaned piglets were investigated. A total of 180 piglets (Duroc × Yorkshire × Landrace) were randomly assigned to 5 dietary treatments and fed a basal diet supplemented with 0 (control), 100, 500, 1000, and 2000 mg chitosan/kg feed, respectively. Results showed that serum AA, prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) contents in piglets were increased in a linear or quadratic dose-dependent manner with increasing chitosan on day 28 (P < 0.05). Chitosan increased serum cytosolic-phospholipase A2 (cPLA2) activity in a linear or quadratic dose-dependent manner on day 14 or 28, and improved 5-lipoxygenase (5-LOX) activity in a linear manner and cyclooxygenase-2 (COX-2) activity quadratically on day 28 (P < 0.05). Moreover, chitosan elevated gene expression of cPLA2 mRNA quadratically in the small intestine on days 14 and 28, increased the COX-2 mRNA expression in the duodenum or jejunum in a linear or quadratic manner on day 28, and improved the 5-LOX mRNA expression quadratically in the small intestine (P < 0.05). These results implied that the metabolism of AA was regulated by chitosan in a dose-dependent relationship, which may be one reason why chitosan affected immune function via AA pathway in weaned piglets.

scholarly journals High-glucose-induced metallothionein expression in endothelial cells: an endothelin-mediated mechanism

2001 ◽  
Vol 281 (3) ◽  
pp. C899-C907 ◽  
Author(s):  
Margarita D. Apostolova ◽  
Shali Chen ◽  
Subrata Chakrabarti ◽  
M. George Cherian
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Mrna Expression ◽  
High Glucose ◽  
Umbilical Vein ◽  
Cell Permeability ◽  
Extracellular Glucose ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Dependent Pathway

Vascular endothelial cells are constantly exposed to oxidative stress and must be protected by physiological responses. In diabetes mellitus, endothelial cell permeability is impaired and may be increased by high extracellular glucose concentrations. It has been postulated that metallothionein (MT) can protect endothelial cells from oxidative stress with its increased expression by cytokines, thrombin, and endothelin (ET)-1. In this study, we demonstrate that high glucose concentration can induce MT expression in endothelial cells through a distinct ET-dependent pathway. Exposure of human umbilical vein endothelial cells (HUVEC) to increasing concentrations of glucose resulted in a rapid dose-dependent increase in MT-2 and ET-1 mRNA expression. MT expression may be further augmented with addition of ET-1. Preincubation of the cells with the specific ETB antagonist BQ-788 blocked MT-2 mRNA expression more effectively than the ETA inhibitor TBC-11251. High glucose also increased immunoreactive MT protein expression and induced translocation of MT into the perinuclear area. Perinuclear localization of MT was related to high-glucose-induced reorganization of F-actin filaments. These results demonstrate that an increase in extracellular glucose in HUVEC can lead to a rapid dose-dependent increase in MT-2 mRNA expression and to perinuclear localization of MT protein with changes to the cytoskeleton. These effects are mediated via the ET receptor-dependent pathway.

scholarly journals Vitamin E enhances the acylation of 1-O-alkyl-sn-glycero-3-phosphocholine in human endothelial cells

1994 ◽  
Vol 298 (1) ◽  
pp. 115-119 ◽  
Author(s):  
K Tran ◽  
A F D'Angelo ◽  
P C Choy ◽  
A C Chan
Keyword(s):  
Endothelial Cells ◽  
Vitamin E ◽  
Platelet Activating Factor ◽  
Enzyme Substrate ◽  
Cell Homogenate ◽  
Transacylase Activity ◽  
Dose Dependent ◽  
Phospholipid Pool ◽  
Indirect Stimulation

1-O-Alkyl-2-acyl-sn-glycero-3-phosphocholine (alkylacyl-GPC) is the precursor of platelet-activating factor. It is formed via the CoA-independent transacylase reaction, which transfers the polyenoyl acyl group from the sn-2 position of a diacyl phospholipid to the sn-2 position of 1-O-alkyl-sn-glycero-3-phosphocholine (alkyl-GPC). We have reported previously that vitamin E alters phospholipid turnover in the endothelial cells by increasing arachidonic acid release and prostacyclin synthesis. In the present study, the role of vitamin E in the formation of alkylacyl-GPC was investigated. Incubation of endothelial cells with vitamin E resulted in an increase in the formation of [3H]alkylacyl-GPC from [3H]alkyl-GPC. The effect of vitamin E was dose-dependent at concentrations below 23 microM. However, vitamin E did not have a direct effect on the transacylase activity. When endothelial cells were incubated with vitamin E, the CoA-independent transacylase activity in the cell homogenate was found to be enhanced. Kinetic analysis of the transacylase activity in the pre-incubated cells showed that the enhancement of enzyme activity was at the enzyme-substrate level. When endothelial cells were incubated with vitamin E analogues (Trolox, tocol and tocopherol acetate), only limited enhancement of the transacylation process was detected. It is clear that vitamin E enhanced the synthesis of alkylacyl-GPC from alkyl-GPC in a very specific manner by an indirect stimulation of the CoA-independent transacylase activity. The regulation by vitamin E of the formation of alkylacyl-GPC may mediate the transfer of arachidonate from the diacyl phospholipid pool into the ether-linked phospholipid pool.

Coordinate regulation of endothelin and adrenomedullin secretion by oxidative stress in endothelial cells

2001 ◽  
Vol 281 (3) ◽  
pp. H1364-H1371 ◽  
Author(s):  
Takatoshi Saito ◽  
Hiroshi Itoh ◽  
Tae-Hwa Chun ◽  
Yasutomo Fukunaga ◽  
Jun Yamashita ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Mrna Expression ◽  
Vascular Diseases ◽  
Transcriptional Level ◽  
Dependent Manner ◽  
Camp Pathway ◽  
Intracellular Ca ◽  
Dose Dependent Fashion ◽  
Dose Dependent

To elucidate the significance of oxidative stress in the modulation of endothelial functions, we examined the effects of H2O2 on the expression of two endothelium-derived vasoactive peptides, endothelin (ET) and adrenomedullin (Am), and their interaction. H2O2 dose dependently suppressed ET secretion and ET-1 mRNA expression in bovine carotid endothelial cells (ECs). Menadion sodium bisulfate, a redox cycling drug, also decreased ET secretion in a dose-dependent manner. Catalase, a H2O2 reductase, and dl-α-tocopherol (vitamin E) significantly inhibited H2O2-induced suppression of ET secretion. Downregulation of ET-1 mRNA under oxidative stress was regulated at the transcriptional level. In contrast, H2O2increased Am secretion (and its mRNA expression) accompanied by the augmentation of cAMP production. Am, as well as 8-bromo-cAMP and forskolin decreased ET secretion in a dose-dependent fashion. Furthermore, an anti-Am monoclonal antibody that we developed abolished H2O2-induced suppression of ET secretion at 6–24 h after the addition of H2O2. H2O2 increased the intracellular Ca2+ concentration ([Ca2+]i). Moreover, treatment with ionomycin, a Ca2+ ionophore, and thapsigargin, an inhibitor of endoplasmic reticulum ATPase, decreased ET secretion dose dependently for 3 h. These results suggest that the production of ET was decreased via activation of the Am-cAMP pathway and by the elevation of [Ca2+]i under oxidative stress. These findings elucidate the coordinate expression of two local vascular hormones, ET and Am, under oxidative stress, which may protect against vascular diseases.

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