References of "Oury, Cécile"
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See detailOverexpression of CD39 in mouse airways promotes bacteria induced inflammation
Theatre, Emilie ULg; Frederix, Kim; Guilmain, William et al

in Journal of Immunology (2012), 189(4), 1966-1974

In airways, the ecto-nucleoside triphosphate diphosphohydrolase CD39 plays a central role in the regulation of physiological mucosal nucleotide concentrations and likely contributes to the control of ... [more ▼]

In airways, the ecto-nucleoside triphosphate diphosphohydrolase CD39 plays a central role in the regulation of physiological mucosal nucleotide concentrations and likely contributes to the control of inflammation because accelerated ATP metabolism occurs in chronic inflammatory lung diseases.We sought to determine whether constant elevated CD39 activity in lung epithelia is sufficient to cause inflammation and whether this affects the response to acute LPS or Pseudomonas aeruginosa exposure. We generated transgenic mice overexpressing human CD39 under the control of the airway-specific Clara cell 10-kDa protein gene promoter. Transgenic mice did not develop any spontaneous lung inflammation. However, intratracheal instillation of LPS resulted in accelerated recruitment of neutrophils to the airways of transgenic mice. Macrophage clearance was delayed, and the amounts of CD8+ T and B cells were augmented. Increased levels of keratinocyte chemoattractant, IL-6, and RANTES were produced in transgenic lungs. Similarly, higher numbers of neutrophils and macrophages were found in the lungs of transgenic mice infected with P. aeruginosa, which correlated with improved bacteria clearance. The transgenic phenotype was partially and differentially restored by coinstillation of P2X1 or P2X7 receptor antagonists or of caffeine with LPS. Thus, a chronic increase of epithelial CD39 expression and activity promotes airway inflammation in response to bacterial challenge by enhancing P1 and P2 receptor activation. [less ▲]

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See detailAMP-activated protein kinase controls liposaccharide-induced hyperpermeability
Castanares-Zapatero, Diego; Overtus, M; Communi, Didier et al

in Critical Care (2012, March), 16(suppl 1), 17

Organ dysfunction determines the severity of sepsis and is correlated to mortality. Endothelial increased permeability contributes to the development of organ failure. AMP-activated protein kinase (AMPK ... [more ▼]

Organ dysfunction determines the severity of sepsis and is correlated to mortality. Endothelial increased permeability contributes to the development of organ failure. AMP-activated protein kinase (AMPK) has been shown to modulate cytoskeleton and could mediate endothelial permeability. Our hypothesis is that AMPK controls sepsis-induced hyperpermeability in the heart and is involved in septic cardiomyopathy. Sepsis was induced by intraperitoneal injection of liposaccharide, 10 mg/kg (LPS). Alpha-1 AMPK knockout mice (α1KO) were compared with wild-type. Vascular permeability was characterized by Evans blue extravasation. Inflammatory cytokine mRNA expression was determined by qPCR analysis. Left ventricular mass was assessed by echocardiography. In addition, to emphasize the beneficial role of AMPK on heart vascular permeability, AMPK activator (acadesine) was administered to C57Bl6 mice before LPS injection. The ANOVA test with Bonferroni's post hoc test and the log-rank test were used. P < 0.05 was considered as significant. Increased cardiac vascular permeability was observed in the LPS group in comparison to untreated animals (2.5% vs. 16%; P < 0.05). The α1KO mice exhibited an increase vascular permeability after LPS injection in comparison to wild-type mice (41.5% vs. 16%; P < 0.05). α1KO animals had a significant mortality increase after LPS injection (70% vs. 10%; P < 0.05). LPS markedly induced the production of proinflammatory cytokines (TNFα, IL-1β, IL-6) that were significantly higher in the α1KO animals. More importantly, LPS treatment leads to an increased left ventricular mass in the α1KO mice within 24 hours, suggesting the onset of edema. Finally LPS-induced vascular hyperpermeability was greatly reduced after AMPK activation by acadesine (13.2% vs. 40%; P < 0.05). AMPK importantly regulates cardiac vascular permeability and could control the sepsis-induced cardiomyopathy. AMPK could represent a new pharmacological target of sepsis. [less ▲]

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See detailATP-gated P2X1 ion channels protect from endotoxemia by dampening neutrophil activation
Lecut, Christelle ULg; Faccinetto, Céline ULg; Delierneux, Céline ULg et al

in Journal of Thrombosis and Haemostasis [=JTH] (2012), 10(3), 453-65

Background: In sepsis, extracellular ATP, secreted by activated platelets and leukocytes, may contribute to the crosstalk between hemostasis and inflammation. Previously, we showed that, in addition to ... [more ▼]

Background: In sepsis, extracellular ATP, secreted by activated platelets and leukocytes, may contribute to the crosstalk between hemostasis and inflammation. Previously, we showed that, in addition to their role in platelet activation, ATP-gated P2X1 ion channels are involved in promoting neutrophil chemotaxis. <br />Objectives: To elucidate the contribution of P2X1 ion channels to sepsis and associated disturbance of hemostasis. <br />Methods: We used P2X1-/- mice in a model of lipopolysaccharide (LPS)-induced sepsis. Hemostasis and inflammation parameters were analysed together with outcome. Mechanisms were further studied ex vivo using mouse and human blood or isolated neutrophils and monocytes. <br />Results: P2X1-/- mice were more susceptible to LPS-induced shock than wild-type mice despite normal cytokine production. Plasma levels of thrombin-antithrombin complexes were higher, thrombocytopenia was worsened and whole blood coagulation time was markedly reduced, pointing to aggravated hemostasis disturbance in the absence of P2X1. However, whole blood platelet aggregation occurred normally and P2X1-/- macrophages displayed normal levels of total tissue factor activity. We found that P2X1-/- neutrophils produced higher amounts of reactive oxygen species. Increased amounts of myeloperoxidase were released in the blood of LPS-treated P2X1-/- mice, and circulating neutrophils and monocytes expressed higher levels of CD11b. Neutrophil accumulation into the lungs was also significantly augmented, as was lipid peroxidation in the liver. Desensitization of P2X1 ion channels led to increased activation of human neutrophils and enhanced formation of platelet-leukocyte aggregates. [less ▲]

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See detailLack of P2X1 ion channels increases endotoxemia associated coagulation and organ damage through neutrophil hyperresponsiveness.
Lecut, Christelle ULg; Faccinetto, Céline ULg; Evans, Richard J et al

in Journal of Thrombosis and Haemostasis [=JTH] (2011), 9(suppl S2),

ATP-gated P2X1 ion channels contribute to arterial thrombosis by amplifying platelet activation. In the search for novel anti-platelet strategies, targeting P2X1 ion channels is appealing. However, in ... [more ▼]

ATP-gated P2X1 ion channels contribute to arterial thrombosis by amplifying platelet activation. In the search for novel anti-platelet strategies, targeting P2X1 ion channels is appealing. However, in this study we found that lack or inhibition of P2X1 channels enhanced neutrophil respiratory burst activity ex vivo. <br />To study the consequence of P2X1 deficiency on neutrophil function in vivo, P2X1-/- mice were used in a model of endotoxin-induced sepsis. Upon injection of lipopolysaccharides (LPS), plasma myeloperoxidase (MPO) concentrations reached higher levels in the P2X1-/- mice, and circulating neutrophils expressed higher levels of surface CD11b compared to wild-type mice. Neutrophil relocalization into the lungs of LPS-treated P2X1-/- mice was also significantly augmented, reflecting a higher activation state of P2X1-/- neutrophils under conditions of sepsis. Accordingly, more extensive lipid peroxidation was observed in the liver of LPS-treated P2X1-/- mice, indicative of exaggerated oxidative damage. Concomitantly, the levels of thrombin-antithrombin complexes were higher in the plasma of LPS-treated P2X1-/- mice and thrombocytopenia was worsened as compared to wild type mice. Elevated numbers of microthrombi were also found in the lungs of these mice. These observations coincided with a higher susceptibility of P2X1-/- mice to LPS-induced septic shock than wild type animals. <br />Our results strongly suggest that P2X1 ion channels play a protective role in sepsis by negatively regulating systemic neutrophil activation, thereby limiting oxidative damage, activation of coagulation and platelet accumulation into the lungs. Therefore, since antagonists of P2X1 ion channels may not only target platelets but also affect neutrophils, inhibiting these channels in the highly inflammatory environment of severe sepsis or of acute coronary syndromes might be detrimental. [less ▲]

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See detailA P2X Ion Channel-triggered NF-{kappa}B Pathway Enhances TNF-{alpha}-induced IL-8 Expression in Airway Epithelial Cells.
Theatre, Emilie ULg; Bours, Vincent ULg; Oury, Cécile ULg

in American Journal of Respiratory Cell and Molecular Biology (2009)

Extracellular ATP, acting at P2Y and P2X receptors, has recently been shown to contribute to airway inflammation. Using different epithelial cell models, this study shows that ATP promotes TNF-alpha ... [more ▼]

Extracellular ATP, acting at P2Y and P2X receptors, has recently been shown to contribute to airway inflammation. Using different epithelial cell models, this study shows that ATP promotes TNF-alpha-elicited IL-8 expression through P2X ion channel-triggered Ca(2+) entry, leading to CaMK-dependent IKK activation and binding of active p65 to IL-8 gene promoter. [less ▲]

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See detailP2X1 Ion Channels Promote Neutrophil Chemotaxis through Rho Kinase Activation
Lecut, Christelle ULg; Frederix, Kim ULg; Johnson, Daniel M et al

in Journal of Immunology (2009)

This study shows that activation of P2X1 ion channels by ATP promotes neutrophil chemotaxis, a process involving Rho kinase-dependent actomyosin-mediated contraction at the cell rear. These ion channels ... [more ▼]

This study shows that activation of P2X1 ion channels by ATP promotes neutrophil chemotaxis, a process involving Rho kinase-dependent actomyosin-mediated contraction at the cell rear. These ion channels may therefore play a significant role in host defense and inflammation. [less ▲]

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See detailContribution of ATP-gated P2X1 ion channels to the control of neutrophil chemotaxis.
Lecut, Christelle ULg; Frederix, Kim ULg; Johnson, Daniel et al

in Purinergic Signalling (2008), 4

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See detailSensitivity of intestinal fibroblasts to TNF-related apoptosis-inducing ligand-mediated apoptosis in Crohn's disease
Reenaers, Catherine ULg; Franchimont, Nathalie; Oury, Cécile ULg et al

in Scandinavian Journal of Gastroenterology (2008), 43

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See detailFurther insights in the mechanisms of interleukin-1beta stimulation of osteoprotegerin in osteoblast-like cells
Lambert, Cécile ULg; Oury, Cécile ULg; Dejardin, Emmanuel ULg et al

in Journal of Bone and Mineral Research (2007), 22(9), 1350-1361

The mechanisms of IL-1beta stimulation of OPG were studied in more detail. Whereas p38 and ERK activation was confirmed to be needed, NF-kappaB was not necessary for this regulation. We also found that ... [more ▼]

The mechanisms of IL-1beta stimulation of OPG were studied in more detail. Whereas p38 and ERK activation was confirmed to be needed, NF-kappaB was not necessary for this regulation. We also found that OPG production after IL-1beta stimulation was not sufficient to block TRAIL-induced apoptosis in MG-63 cells. INTRODUCTION: Osteoprotegerin (OPG) plays a key role in the regulation of bone resorption and is stimulated by interleukin (IL)-1beta. Herein, we defined the mechanisms of IL-1beta stimulation of OPG focusing on the potential involvement of MAPK and NF-kappaB. We also examined whether OPG production in response to IL-1beta influences TRAIL-induced apoptosis in MG-63 cells. MATERIALS AND METHODS: OPG mRNA levels in MG-63 cells were quantified by real-time RT-PCR and protein levels of OPG and IL-6 by ELISA. Cell viability was assessed using the methyltetrazidium salt (MTS) reduction assay. The role of the MAPK pathway was studied by both Western blotting and the use of specific chemical inhibitors. NF-kappaB function was studied using BAY 11-7085 and by siRNA transfection to inhibit p65 synthesis. Transcription mechanisms were analyzed by transiently transfecting MG-63 cells with OPG promoter constructs. Post-transcriptional effects were examined by using cycloheximide and actinomycin D. RESULTS: MG-63 cells treatment with IL-1beta resulted in the phosphorylation of c-Jun NH(2)-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK). The use of the specific inhibitors showed that p38 and ERK but not JNK were needed for IL-1beta-induced OPG production. In contrast, NF-kappaB was not essential for IL-1beta induction of OPG. We also showed a small transcriptional and a possible post-transcriptional or translational regulation of OPG by IL-1beta. Exogenous OPG blocked TRAIL-induced apoptosis, but IL-1beta induction of OPG did not influence TRAIL-induced cell death. CONCLUSIONS: IL-1beta stimulates OPG production by mechanisms dependent on p38 and ERK. In contrast, NF-kappaB was not essential for this regulation. Although the relevance of IL-1beta stimulation of OPG is still not fully understood, our data showed that IL-1beta stimulation of OPG does not modify TRAIL-induced cell death. [less ▲]

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See detailEarly inflammation in the airways of a cystic fibrosis foetus
Verhaeghe, C.; Delbecque, Katty ULg; de Leval, Laurence ULg et al

in Journal of Cystic Fibrosis (2007), 6(4), 304-308

In cystic fibrosis patients, inflammation is often considered to be secondary to chronic infections. In the present study, we show increased levels of pro-inflammatory proteins in the lungs of a cystic ... [more ▼]

In cystic fibrosis patients, inflammation is often considered to be secondary to chronic infections. In the present study, we show increased levels of pro-inflammatory proteins in the lungs of a cystic fibrosis foetus compared to the lungs of two normal foetuses. Our findings suggest therefore the existence of an early intrinsic pro-inflammatory state in cystic fibrosis airways. (C) 2006 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved. [less ▲]

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See detailRole of IKK and ERK pathways in intrinsic inflammation of cystic fibrosis airways
Verhaeghe, Catherine ULg; Remouchamps, Caroline ULg; Hennuy, Benoît ULg et al

in Biochemical Pharmacology (2007), 73(12), 1982-1994

in cystic fibrosis (CF) patients, pulmonary inflammation is a major cause of morbidity and mortality and may precede bacterial colonization. The aim of the present study was to investigate the molecular ... [more ▼]

in cystic fibrosis (CF) patients, pulmonary inflammation is a major cause of morbidity and mortality and may precede bacterial colonization. The aim of the present study was to investigate the molecular mechanisms underlying intrinsic inflammation in cystic fibrosis air-ways. Using different cystic fibrosis cell models, we first demonstrated that, beside a high constitutive nuclear factor of kappaB (NF-kappa B) activity, CF cells showed a higher activator protein-1 (AP-1) activity as compared to their respective control cells. Gene expression profiles, confirmed by RT-PCR and ELISA, showed over-expression of numerous NF-KB and AP-1-dependent pro-inflammatory genes in CF cells in comparison with control cells. Activation of NF-KB was correlated with higher inhibitor of kappa B kinase (IKK) activity. In addition, Bio-plex phosphoprotein assays revealed higher extracellular signal-regulated kinase (ERK) phosphorylation in CFT-2 cells. Inhibition of this kinase strongly decreased expression of pro-inflammatory genes coding for growth-regulated proteins (Gro-alpha, Gro-beta and Gro-gamma) and interleukins (IL-1 beta, IL-6 and IL-8). Moreover, inhibition of secreted interleukin-1 beta (IL-1 beta) and basic fibroblast growth factor (bFGF) with neutralizing antibodies reduced pro-inflammatory gene expression. Our data thus demonstrated for the first time that the absence of functional cystic fibrosis transmembrane conductance regulator (CFTR) at the plasma membrane leads to an intrinsic AP-1, in addition to NF-kappa B, activity and consequently to a pro-inflammatory state sustained through autocrine factors such as IL-1 beta and bFGF. (c) 2007 Elsevier Inc. All rights reserved. [less ▲]

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See detailP2X1 receptors as new regulators of neutrophil life span
Faccinetto, Céline ULg; Lecut, Christelle ULg; Jacobs, Nathalie ULg et al

in Journal of Thrombosis and Haemostasis [=JTH] (2007)

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See detailIntrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells
Verhaeghe, Catherine ULg; Tabruyn, Sébastien ULg; Oury, Cécile ULg et al

in Biochemical and Biophysical Research Communications (2007), 356(3), 745-749

Cystic fibrosis is a common genetic disorder characterized by a severe lung inflammation and fibrosis leading to the patient's death. Enhanced angiogenesis in cystic fibrosis (CF) tissue has been ... [more ▼]

Cystic fibrosis is a common genetic disorder characterized by a severe lung inflammation and fibrosis leading to the patient's death. Enhanced angiogenesis in cystic fibrosis (CF) tissue has been suggested, probably caused by the process of inflammation, as similarly described in asthma and chronic bronchitis. The present study demonstrates an intrinsic pro-angiogenic status of cystic fibrosis airway epithelial cells. Microarray experiments showed that CF airway epithelial cells expressed several angiogenic factors such as VEGF-A, VEGF-C, bFGF, and PLGF at higher levels than control cells. These data were confirmed by real-time quantitative PCR and, at the protein level, by ELISA. Conditioned media of these cystic fibrosis cells were able to induce proliferation, migration and sprouting of cultured primary endothelial cells. This report describes for the first time that cystic fibrosis epithelial cells have an intrinsic angiogenic activity. Since excess of angiogenesis is correlated with more severe pulmonary disease, our results could lead to the development of new therapeutic applications. (c) 2007 Elsevier Inc. All rights reserved. [less ▲]

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See detailDe novo C16- and C24-ceramide generation contributes to spontaneous neutrophil apoptosis.
Seumois, Gregory; Fillet, Marianne ULg; Gillet, Laurent ULg et al

in Journal of Leukocyte Biology (2007), 81(6), 1477-1486

Neutrophils rapidly undergo spontaneous apoptosis following their release from the bone marrow. Although central to leukocyte homeostasis, the mechanisms that regulate neutrophil apoptosis remain poorly ... [more ▼]

Neutrophils rapidly undergo spontaneous apoptosis following their release from the bone marrow. Although central to leukocyte homeostasis, the mechanisms that regulate neutrophil apoptosis remain poorly understood. We show here that apoptosis of cultured neutrophils is preceded by a substantial increase in the intracellular levels of 16 and 24 carbon atom (C(16)- and C(24))-ceramides, which are lipid second messengers of apoptosis and stress signaling. Treatment of neutrophils with fumonisin B(2), a selective inhibitor of the de novo pathway of ceramide synthesis, prevented accumulation of C(16)- and C(24)-ceramides. Moreover, fumonisin B(2) significantly reduced caspase-3, -8, and -9 activation and apoptosis in these cells. Conversely, 3-O-methylsphingomyelin and fantofarone, which are specific inhibitors of neutral and acid sphingomyelinases, respectively, neither inhibited C(16)- and C(24)-ceramide production nor decreased the apoptosis rate in neutrophils, indicating that in these cells, ceramides are not generated from membrane sphingomyelin. Further experiments showed that increasing endogenous C(16)- and C(24)-ceramide levels by using DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol and (1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol, two inhibitors of ceramide metabolism, enhances caspase-3, -8, and -9 activity and increases neutrophil apoptosis. Similarly, apoptosis was induced rapidly when synthetic C(16)- and/or C(24)-ceramides were added to neutrophil cultures. Finally, GM-CSF, a cytokine that delays neutrophil apoptosis, abrogated C(16)- and C(24)-ceramide accumulation totally in cultured neutrophils, whereas Fas ligation accelerated apoptosis in these cells without affecting de novo ceramide production. We conclude that de novo generation of C(16)- and C(24)-ceramides contributes to spontaneous neutrophil apoptosis via caspase activation and that GM-CSF exerts its antiapoptotic effects on neutrophils, at least partly through inhibition of ceramide accumulation. [less ▲]

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See detailThe platelet ATP and ADP receptors.
Oury, Cécile ULg; Toth-Zsamboki, Emese; Vermylen, Jos et al

in Current Pharmaceutical Design (2006)

This review focuses on recent findings on the physiology of these platelet ADP and ATP receptors, their distinct downstream intracellular signaling pathways as well as on the available agonists ... [more ▼]

This review focuses on recent findings on the physiology of these platelet ADP and ATP receptors, their distinct downstream intracellular signaling pathways as well as on the available agonists, antagonists and inhibitors that allow their pharmacological discrimination. [less ▲]

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See detailERK2 activation in arteriolar and venular murine thrombosis: platelet receptor GPIb vs. P2X.
Oury, Cécile ULg; Daenens, Kim; Hu, Hu et al

in Journal of Thrombosis and Haemostasis [=JTH] (2006)

The functional significance of extracellular signal-regulated kinase 2 (ERK2) activation was investigated during shear induced human platelet aggregation (SIPA) in vitro and during shear controlled ... [more ▼]

The functional significance of extracellular signal-regulated kinase 2 (ERK2) activation was investigated during shear induced human platelet aggregation (SIPA) in vitro and during shear controlled thrombosis in vivo in intestinal arterioles and venules of wild type (WT) and transgenic (TG) mice with platelet-specific overexpression of human P2X(1) (TG). The conclusions are that P2X(1) and ERK2 both participate in shear stress controlled thrombosis, but ERK2 activation is initiated predominantly via GPIb-VWF interactions. [less ▲]

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See detailPlatelet expression of non-functional P2X1delL ion channels in mice reduces arterial thrombosis
Oury, Cécile ULg; Daenens, Kim; Feijge, Marion et al

in Haematologica (2004)

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