scholarly journals Glucosyltransferases of Viridans Group Streptococci Modulate Interleukin-6 and Adhesion Molecule Expression in Endothelial Cells and Augment Monocytic Cell Adherence

2006 ◽  
Vol 74 (2) ◽  
pp. 1273-1283 ◽  
Author(s):  
Chiou-Yueh Yeh ◽  
Jen-Yang Chen ◽  
Jean-San Chia
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Interleukin 6 ◽  
Umbilical Vein ◽  
Mitogen Activated Protein Kinase ◽  
Free Form ◽  
Dependent Manner ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Viridans Group Streptococci

ABSTRACT Recruitment of monocytes plays important roles during vegetation formation and endocardial inflammation in the pathogenesis of infective endocarditis (IE). Bacterial antigens or modulins can activate endothelial cells through the expression of cytokines or adhesion molecules and modulate the recruitment of leukocytes. We hypothesized that glucosyltransferases (GTFs), modulins of viridans group streptococci, may act directly to up-regulate the expression of adhesion molecules and also interleukin-6 (IL-6) to augment monocyte attachment to endothelial cells. Using primary cultured human umbilical vein endothelial cells (HUVECs) as an in vitro model, we demonstrated that GTFs (in the cell-bound or free form) could specifically modulate the expression of IL-6, and also adhesion molecules, in a dose- and time-dependent manner. Results of inhibition assays suggested that enhanced expression of adhesion molecules was dependent on the activation of nuclear factor κB (NF-κB) and extracellular signal-regulated kinase and that p38 mitogen-activated protein kinase pathways also contributed to the release of IL-6. Streptococcus-infected HUVECs or treatment with purified IL-6 plus soluble IL-6 receptor α enhanced the expression of ICAM-1 and the adherence of the monocytic cell line U937. These results suggest that streptococcal GTFs might play an important role in recruiting monocytic cells during inflammation in IE through induction of adhesion molecules and IL-6, a cytokine involved in transition from neutrophil to monocyte recruitment.

scholarly journals Lipopolysaccharide Activates Caspase-1 (Interleukin-1–Converting Enzyme) in Cultured Monocytic and Endothelial Cells

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 577-584 ◽  
Author(s):  
Ralf R. Schumann ◽  
Claus Belka ◽  
Dirk Reuter ◽  
Norbert Lamping ◽  
Carsten J. Kirschning ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Cysteine Proteases ◽  
Precursor Protein ◽  
Converting Enzyme ◽  
Blood Monocytes ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Caspase 1

Abstract Interleukin-1β (IL-1β) is a pleiotropic proinflammatory cytokine. Mechanisms leading to its secretion include not only release of newly synthesized protein, but also cleavage of a preformed immature precursor protein into an active secretory form by the intracellular protease caspase-1 (formerly termed IL-1–converting enzyme [ICE]). Caspase-1 belongs to a rapidly growing family of cysteine proteases with substrate specificity for aspartate involved in cellular apoptosis. We have used an assay determining the caspase-1 activity based on cleavage of a fluorogenic peptide substrate to elucidate its role in lipopolysaccharide (LPS)-induced secretion of IL-1β. We show that LPS induces moderate caspase-1 activity in the monocytic cell line THP-1, in freshly isolated peripheral blood monocytes, and in human umbilical vein endothelial cells (HUVECs) in a time- and dose-dependent fashion. Caspase-1 activation by LPS was associated with cleavage of the IL-1β precursor protein that was followed by release of the mature IL-1β protein in monocytic cells. In contrast, subsequent release of IL-1β by HUVECs was not significant. LPS-induced caspase-1 activation appeared not to result from modulation of caspase-1 transcript accumulation and inhibition of caspase-1 activity was accomplished by two specific inhibitors, YVAD-CHO and YVAD-CMK, capable of alleviating the release of mature IL-1β. Taken together, these results show that LPS moderately activates caspase-1 and that caspase-1 activation contributes to LPS induction of IL-1β secretion.

Human apolipoprotein A-I induces cyclooxygenase-2 expression and prostaglandin I-2 release in endothelial cells through ATP-binding cassette transporter A1

2011 ◽  
Vol 301 (3) ◽  
pp. C739-C748 ◽  
Author(s):  
Donghui Liu ◽  
Liang Ji ◽  
Xunliang Tong ◽  
Bing Pan ◽  
Jing-Yan Han ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Cyclooxygenase 2 ◽  
Mitogen Activated Protein Kinase ◽  
Atp Binding ◽  
Dependent Manner ◽  
Atp Binding Cassette Transporter ◽  
Apolipoprotein A ◽  
Cox 2 ◽  
Atp Binding Cassette

High-density lipoprotein (HDL) can induce cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release in endothelial cells to exert multiple antiatherogenic functions. This effect has been attributed mainly to the role of sphingosine-1-phosphate (S1P) integrated in HDL. However, whether apolipoprotein A-I (apoA-I), the major apolipoprotein of HDL, could induce COX-2 expression and PGI-2 release still remains unclear. In the present study, we selectively delipidated HDL and confirmed that apoA-I could facilitate COX-2 expression and PGI-2 production in human umbilical vein endothelial cells (HUVECs). ApoA-I, but not trypsinized apoA-I, induced COX-2 expression in a time- and dose-dependent manner consistent with a key role for apoA-I in this process. Additionally, cotreatment of apoA-I with S1P further enhanced COX-2 expression and PGI-2 production in HUVECs. These effects triggered by apoA-I were not inhibited by pertussis toxin, consistent with SIP receptor independent pathway for apoA-I effect. Moreover, we demonstrated that the activation of p38 mitogen-activated protein kinase (MAPK), extracellular receptor kinase (ERK) 1/2, and JAK2 pathways by apoA-I was involved in the expression of COX-2 and the release of PGI-2 in HUVECs, and these effects were inhibited by their specific inhibitors, respectively. Small interfering RNA experiments showed that ATP binding-cassette transporter A1 (ABCA1) was required for COX-2 expression and PGI-2 release induced by apoA-I. Thus our results indicate that apoA-I induces COX-2 expression and PGI-2 release through ABCA1 and the activation of intracellular p38 MAPK, ERK1/2, as well as JAK2 pathways, and apoA-I can reinforce these effects with S1P in HUVECs. These novel effects of apoA-I could in part mediate antiatherogenic effects of HDL.

Anandamide induces apoptosis in human endothelial cells: its regulation system and clinical implications

2003 ◽  
Vol 89 (05) ◽  
pp. 875-884 ◽  
Author(s):  
Kazuyo Yamaji ◽  
Krishna Sarker ◽  
Koichi Kawahara ◽  
Satoshi Iino ◽  
Munekazu Yamakuchi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Crucial Role ◽  
Umbilical Vein ◽  
Mitogen Activated Protein Kinase ◽  
Regulation System ◽  
Dependent Manner ◽  
Vanilloid Receptor 1 ◽  
Mitogen Activated Protein ◽  
Umbilical Vein Endothelial Cells ◽  
Endogenous Cannabinoid

SummaryAnandamide (AEA), an endogenous cannabinoid, is generated by macrophages during shock conditions, and is thought to be a causative mediator of septic shock. Thus, we hypothesized that AEA plays a crucial role in endothelial cell (EC) injury. Here, we demonstrate that AEA induces apoptosis in a time-and dose-dependent manner in human umbilical vein endothelial cells (HUVECs). AEA triggered phosphorylation of c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated protein kinase. AEA also showed a marked increase of interleukin 1β–converting enzyme (ICE)CED-3 family protease (caspase-3) activity. AEA-induced EC death was inhibited by a selective vanilloid receptor 1 (VR1) antagonist, capsazepine, and was enhanced by a VR1 agonist, capsaicin, indicating that AEA induces apoptosis in ECs via VR1. In conclusion, we propose that AEA may play a crucial role in EC injury under conditions of shock, and that the use of inhibitors of the AEA regulation system may have a therapeutic effect under these conditions.

scholarly journals Two sites on P-selectin (the lectin and epidermal growth factor-like domains) are involved in the adhesion of monocytes to thrombin-activated endothelial cells

1994 ◽  
Vol 303 (2) ◽  
pp. 619-624 ◽  
Author(s):  
J F Murphy ◽  
J L McGregor
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Mononuclear Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Activated Platelets ◽  
Epidermal Growth

P-selectin, also known as GMP-140, PADGEM or CD62, is expressed on the surface of thrombin-activated platelets and endothelial cells (EC). It is a member of the selectin family of adhesion molecules that regulate leucocyte interactions with the blood vessel wall. In this study we have found that peptides derived from both the lectin (residues 19-34 and 51-61) and epidermal growth factor (EGF)-like (residues 127-139) domains inhibit the adhesion of peripheral blood mononuclear cells (PBMC), elutriated monocytes and a monocytic cell line (U937) to thrombin-activated EC. This inhibition occurred in a concentration-dependent manner and the peptide most active at the lowest concentrations was the one derived from the EGF-like motif (127-139). The scrambled forms of these peptides, identical in amino acid composition to the authentic peptides but with altered sequences, were not inhibitory. Thrombin-activated platelets supported adhesion of U937 cells and this adhesion was dramatically inhibited by the two peptides derived from the lectin-like domain (residues 19-34 and 51-61). All three peptides, when conjugated to BSA and coated on plastic plates, mediated U937 cell adhesion. This study shows, for the first time, that two sites on P-selectin, the lectin and EGF-like domains, are involved in the adhesion of monocytes to thrombin-activated EC.

scholarly journals Oxidized low-density lipoprotein induces the expression of P-selectin (GMP140/PADGEM/CD62) on human endothelial cells

1995 ◽  
Vol 306 (1) ◽  
pp. 293-298 ◽  
Author(s):  
V Gebuhrer ◽  
J F Murphy ◽  
J C Bordet ◽  
M P Reck ◽  
J L McGregor
Keyword(s):  
Monoclonal Antibody ◽  
Endothelial Cells ◽  
Mononuclear Cells ◽  
Umbilical Vein ◽  
Oxidized Ldl ◽  
Low Density ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Ldl Particles ◽  
High Concentrations

It is now well established that monocytes adhere to endothelial cells activated by oxidized low-density lipoproteins (LDL). However, the adhesive receptors on endothelial cells involved in binding monocytes, following an insult by oxidized LDL, remains to be elucidated. In this study we have looked at the effect of native or oxidized LDL on the expression of P-selectin. Native LDL (N-LDL) was oxidized by incubation with either endothelial cells (EC-LDL) or copper (Cu-LDL), or in culture medium as a control (C-LDL). Expression of P-selectin was assayed with an anti-P-selectin (CD62) monoclonal antibody (LYP20). Results show that EC-LDL and Cu-LDL, but not N-LDL or C-LDL, induce the expression of P-selectin by human umbilical-vein endothelial cells (HUVECs). Induction of P-selectin by low concentrations (20 micrograms/ml) of LDL is directly related to the state of oxidation of the LDL particles. In addition, high concentrations (100 micrograms/ml) of N-LDL also activate HUVECs by inducing P-selectin expression. This expression was sustained for a period of over 1 h on LDL-activated endothelial cells, in contrast with thrombin- or histamine-activated endothelial cells, whose P-selectin levels fall within 15-20 min after induction. E-selectin, in contrast with P-selectin, could not be induced by endothelial cells treated with low or high concentrations of oxidized LDL. Results in this study show that P-selectin expressed by oxidized-LDL-treated endothelial cells are involved in mediating the adhesion of a monocytic cell line (U937) or monocytes in peripheral-blood mononuclear cells. An anti-P-selectin monoclonal antibody (LYP20) inhibited the binding of U937 cells and monocytes. These results strongly suggest that P-selectin is involved in the early stages of atherogenesis.

scholarly journals C-Terminal Repeats of Clostridium difficile Toxin A Induce Production of Chemokine and Adhesion Molecules in Endothelial Cells and Promote Migration of Leukocytes

2007 ◽  
Vol 76 (3) ◽  
pp. 1170-1178 ◽  
Author(s):  
Chiou-Yueh Yeh ◽  
Chun-Nan Lin ◽  
Chuan-Fa Chang ◽  
Chun-Hung Lin ◽  
Huei-Ting Lien ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Biological Activity ◽  
Clostridium Difficile ◽  
Adhesion Molecules ◽  
Mononuclear Cells ◽  
Umbilical Vein ◽  
Biologically Active ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Toxin A

ABSTRACT The C-terminal repeating sequences of Clostridium difficile toxin A (designated ARU) are homologous to the carbohydrate-binding domain of streptococcal glucosyltransferases (GTFs) that were recently identified as potent modulins. To test the hypothesis that ARU might exert a similar biological activity on endothelial cells, recombinant ARU (rARU), which was noncytotoxic to cell cultures, was analyzed using human umbilical vein endothelial cells. The rARU could bind directly to endothelial cells in a serum- and calcium-dependent manner and induce the production of interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein 1 in a dose-dependent manner. An oligosaccharide binding assay indicated that rARU, but not GTFC, binds preferentially to Lewis antigens and 3′HSO3-containing oligosaccharides. Binding of rARU to human endothelial or intestinal cells correlated directly with the expression of Lewis Y antigen. Bound rARU directly activated mitogen-activated protein kinases and the NF-κB signaling pathway in endothelial cells to release biologically active chemokines and adhesion molecules that promoted migration in a transwell assay and the adherence of polymorphonuclear and mononuclear cells to the endothelial cells. These results suggest that ARU may bind to multiple carbohydrate motifs to exert its biological activity on human endothelial cells.

Antiinflammatory activity of astragaloside IV is mediated by inhibition of NF-κB activation and adhesion molecule expression

2003 ◽  
Vol 90 (11) ◽  
pp. 904-914 ◽  
Author(s):  
Wei-Jian Zhang ◽  
Peter Hufnagl ◽  
Bernd Binder ◽  
Johann Wojta
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Nuclear Translocation ◽  
Specific Cell ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Astragaloside Iv ◽  
Monocytic Cell ◽  
Induced Expression ◽  
Anti Inflammatory

SummaryThe regulated expression of adhesion molecules on the surface of endothelial cells is a key process in the pathogenesis of inflammation. The saponin astragaloside IV (AS-IV), a 3-O-β-D-xylopyranosyl-6-O-β-D-glucopyranosylcycloastragenol purified from the Chinese medical herb Astragalus membranaceus(Fisch) Bge.has been shown to have anti-inflammatory effects in vivo.In this study we have investigated the effect of AS-IV on cytokine-and LPS-stimulated expression of adhesion molecules in and leukocyte adhesion to endothelial cells. We have demonstrated that AS-IV significantly reduced the adhesion promoting activity of LPS-stimulated HUVECs for polymorph-nuclear leukocytes (PMNs) and the monocytic cell line THP-1. Furthermore, by using specific cell ELISAs we could show that AS-IV decreased the LPS-induced expression of E-selectin and VCAM-1 on the surface of HUVECs in a dose and time dependent manner, whereas the expression of ICAM-1 was not affected by AS-IV. AS-IV also inhibits TNFβ-induced VCAM-1 expression. The saponin octyl-D-glucopyranoside had no effect on the LPS-induced expression of E-selectin and VCAM-1 excluding an unspecific detergent-like effect of AS-IV. Moreover, AS-IV significantly inhibited LPS- and TNFβ-induced specific mRNA levels for E-selectin and VCAM-1. Finally, we could show that AS-IV completely abolished LPS- and TNFα-induced nuclear translocation of NF-κB and NF-κB DNA binding activity in endothelial cells. We conclude that the ability of AS-IV to inhibit the NF-κB pathway might be one underlying mechanism contributing to its anti-inflammatory potential in vivo.

scholarly journals Lipopolysaccharide Activates Caspase-1 (Interleukin-1–Converting Enzyme) in Cultured Monocytic and Endothelial Cells

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 577-584 ◽  
Author(s):  
Ralf R. Schumann ◽  
Claus Belka ◽  
Dirk Reuter ◽  
Norbert Lamping ◽  
Carsten J. Kirschning ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Interleukin 1 ◽  
Cysteine Proteases ◽  
Precursor Protein ◽  
Converting Enzyme ◽  
Blood Monocytes ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Caspase 1

Interleukin-1β (IL-1β) is a pleiotropic proinflammatory cytokine. Mechanisms leading to its secretion include not only release of newly synthesized protein, but also cleavage of a preformed immature precursor protein into an active secretory form by the intracellular protease caspase-1 (formerly termed IL-1–converting enzyme [ICE]). Caspase-1 belongs to a rapidly growing family of cysteine proteases with substrate specificity for aspartate involved in cellular apoptosis. We have used an assay determining the caspase-1 activity based on cleavage of a fluorogenic peptide substrate to elucidate its role in lipopolysaccharide (LPS)-induced secretion of IL-1β. We show that LPS induces moderate caspase-1 activity in the monocytic cell line THP-1, in freshly isolated peripheral blood monocytes, and in human umbilical vein endothelial cells (HUVECs) in a time- and dose-dependent fashion. Caspase-1 activation by LPS was associated with cleavage of the IL-1β precursor protein that was followed by release of the mature IL-1β protein in monocytic cells. In contrast, subsequent release of IL-1β by HUVECs was not significant. LPS-induced caspase-1 activation appeared not to result from modulation of caspase-1 transcript accumulation and inhibition of caspase-1 activity was accomplished by two specific inhibitors, YVAD-CHO and YVAD-CMK, capable of alleviating the release of mature IL-1β. Taken together, these results show that LPS moderately activates caspase-1 and that caspase-1 activation contributes to LPS induction of IL-1β secretion.

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