References of "Bureau, Fabrice"
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See detailIr-LBP, an ixodes ricinus tick salivary LTB4-binding lipocalin, interferes with host neutrophil function.
Beaufays, Jérôme ULg; Adam, Benoit; Menten-Dedoyart, Catherine ULg et al

in PLoS ONE (2008), 3(12), 3987

BACKGROUND: During their blood meal, ticks secrete a wide variety of proteins that can interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation ... [more ▼]

BACKGROUND: During their blood meal, ticks secrete a wide variety of proteins that can interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: We previously identified 14 new lipocalin genes in the tick Ixodes ricinus. One of them codes for a protein that specifically binds leukotriene B4 with a very high affinity (Kd: +/-1 nM), similar to that of the neutrophil transmembrane receptor BLT1. By in silico approaches, we modeled the 3D structure of the protein and the binding of LTB4 into the ligand pocket. This protein, called Ir-LBP, inhibits neutrophil chemotaxis in vitro and delays LTB4-induced apoptosis. Ir-LBP also inhibits the host inflammatory response in vivo by decreasing the number and activation of neutrophils located at the tick bite site. Thus, Ir-LBP participates in the tick's ability to interfere with proper neutrophil function in inflammation. CONCLUSIONS/SIGNIFICANCE: These elements suggest that Ir-LBP is a "scavenger" of LTB4, which, in combination with other factors, such as histamine-binding proteins or proteins inhibiting the classical or alternative complement pathways, permits the tick to properly manage its blood meal. Moreover, with regard to its properties, Ir-LBP could possibly be used as a therapeutic tool for illnesses associated with an increased LTB4 production. [less ▲]

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See detailUsing a human microarray to highlight new genes of interest for a better understanding of molecular mechanisms that underpin the physiopathology of heaves
Ramery, Eve ULg; Closset, Rodrigue; Bureau, Fabrice ULg et al

in Proceedings: Plant and Animal Genome Conference, Equine Workshop, San Diego (2008)

Environmental causes of heaves are well described, but the molecular mechanisms of the disease remain unclear. Using reverse transcription polymerase chain reaction (RT-PCR), disparate results have been ... [more ▼]

Environmental causes of heaves are well described, but the molecular mechanisms of the disease remain unclear. Using reverse transcription polymerase chain reaction (RT-PCR), disparate results have been obtained concerning cytokines expression profile. cDNA microarray appears to be so far the platform of choice for massively parallel gene expression profiling and provides a good tool for exploratory research. However, equine-specific microarrays are not yet available on the market. Because they are commercially available, highly specific and well annotated, human and mouse large-scale microarrays are an exploratory alternative to equine-specific microarrays. In the present study, the purpose was to highlight new targets not previously related to the disease and able to improve our understanding of the molecular mechanisms of the disease. A human microarray was used to study gene expression in nucleated cells originating from peripheral blood and bronchoalveolar lavage fluid in heaves-affected horses. With a four-fold cut-off, a total of 46 candidates were identified with differentially regulated genes between heaves-affected horses and controls. Based on their documented function, five of these genes were selected for the real-time quantitative RT-PCR (RT-qPCR) validation procedure: CYBB, BTG1, MARCKS, PTX3 and PTPRC. The RT-qPCR results confirmed those obtained with the microarray, pointing out these genes as new directions for future experiments. However, the human microarray failed to detect the presence of IL-1beta and Il-8, otherwise confirmed by RT-qPCR, and the expression profile of the disease could not be obtained [less ▲]

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See detailAnti-inflammatory effects of ipratropium bromide in rats with cadmium-induced acute pulmonary inflammation
Zhang, W.; Fievez, Laurence ULg; Cheu, Esteban ULg et al

in Proceedings of the 12th Annual Meeting of the French Society of Pharmacology and Therapeutics (2008)

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See detailRole of beta 2-receptors in the anti-inflammatory effects of formoterol in rats with cadmium-induced acute pulmonary inflammation
Zhang, W.; Fievez, Laurence ULg; Cheu, Esteban ULg et al

in Fundamental & Clinical Pharmacology (2008), 227

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See detailHunting for a key to the enigma of heaves in the black box of the white cells
Art, Tatiana ULg; Bureau, Fabrice ULg; Robinson, N Edward

in Veterinary Journal (2008), 177(3), 307-308

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See detailDendritic cells genetically engineered to express IL-10 induce long-lasting antigen-specific tolerance in experimental asthma.
Henry, E.; Desmet, Christophe ULg; Garze, V. et al

in Journal of Immunology (2008), 181(10), 7230-7242

Dendritic cells (DCs) are professional APCs that have a unique capacity to initiate primary immune responses, including tolerogenic responses. We have genetically engineered bone marrow-derived DCs to ... [more ▼]

Dendritic cells (DCs) are professional APCs that have a unique capacity to initiate primary immune responses, including tolerogenic responses. We have genetically engineered bone marrow-derived DCs to express the immunosuppressive cytokine IL-10 and tested the ability of these cells to control experimental asthma. A single intratracheal injection of OVA-pulsed IL-10-transduced DCs (OVA-IL-10-DCs) to naive mice before OVA sensitization and challenge prevented all of the cardinal features of airway allergy, namely, eosinophilic airway inflammation, airway hyperreactivity, and production of mucus, Ag-specific Igs, and IL-4. OVA-IL-10-DCs also reversed established experimental asthma and had long-lasting and Ag-specific effects. We furthermore showed, by using IL-10-deficient mice, that host IL-10 is required for mediating the immunomodulatory effects of OVA-IL-10-DCs and demonstrated a significant increase in the percentage of OVA-specific CD4(+)CD25(+)Foxp3(+)IL-10(+) regulatory T cells in the mediastinal lymph nodes of OVA-IL-10-DC-injected mice. Finally, adoptive transfer of CD4(+) mediastinal lymph node T cells from mice injected with OVA-IL-10-DCs protected OVA-sensitized recipients from airway eosinophilia upon OVA provocation. Our study describes a promising strategy to induce long-lasting Ag-specific tolerance in airway allergy. [less ▲]

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See detailRelevance of using a human microarray to study gene expression in heaves-affected horses.
Ramery, Eve ULg; Closset, Rodrigue; Bureau, Fabrice ULg et al

in Veterinary Journal (2008), 177(2), 216-221

Environmental causes of heaves are well described, but the molecular mechanisms of the disease remain unclear. Previous studies have highlighted the implications of variations in gene expression, most ... [more ▼]

Environmental causes of heaves are well described, but the molecular mechanisms of the disease remain unclear. Previous studies have highlighted the implications of variations in gene expression, most using reverse transcription polymerase chain reaction (RT-PCR). This well-known technique limits the number of genes that can be studied in a single assay. Microarray appears to be a valuable tool to by-pass this limitation, but so far there has been no equine-specific microarray available on the market. The present study was performed to determine whether a human microarray could be used to study gene expression in nucleated cells originating from peripheral blood and bronchoalveolar lavage fluid (BALF) in heaves-affected horses. With a four-fold cut-off, a total of 46 candidates were identified with differentially regulated genes between heaves-affected horses and controls. A real-time quantitative RT-PCR (RT-QPCR) conducted on a selection of genes, determined on the basis of previous publications, was used to validate the microarray results. The microarray failed to detect the presence of interleukin (IL)-1beta and IL-8 mRNA in the nucleated cells from BALF otherwise confirmed by real-time RT-QPCR. Although some candidate genes have been identified using this method, a complete expression profile of genes related to heaves could not be obtained with the use of the human microarray. [less ▲]

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See detailNicotinamide phosphoribosyl transferase/pre-B cell colony-enhancing factor/visfatin is required for lymphocyte development and cellular resistance to genotoxic stress.
Rongvaux, Anthony; Galli, Mara; Denanglaire, Sebastien et al

in Journal of Immunology (2008), 181(7), 4685-4695

Nicotinamide phosphoribosyl transferase (Nampt)/pre-B cell colony-enhancing factor (PBEF)/visfatin is a protein displaying multiple functional properties. Originally described as a cytokine-like protein ... [more ▼]

Nicotinamide phosphoribosyl transferase (Nampt)/pre-B cell colony-enhancing factor (PBEF)/visfatin is a protein displaying multiple functional properties. Originally described as a cytokine-like protein able to regulate B cell development, apoptosis, and glucose metabolism, this protein also plays an important role in NAD biosynthesis. To gain insight into its physiological role, we have generated a mouse strain expressing a conditional Nampt allele. Lack of Nampt expression strongly affects development of both T and B lymphocytes. Analysis of hemizygous cells and in vitro cell lines expressing distinct levels of Nampt illustrates the critical role of this protein in regulating intracellular NAD levels. Consequently, a clear relationship was found between intracellular Nampt levels and cell death in response to the genotoxic agent MNNG (N-methyl-N'-nitro-N-nitrosoguanidine), confirming that this enzyme represents a key regulator of cell sensitivity to NAD-consuming stress secondary to poly(ADP-ribose) polymerases overactivation. By using mutant forms of this protein and a well-characterized pharmacological inhibitor (FK866), we unequivocally demonstrate that the ability of the Nampt to regulate cell viability during genotoxic stress requires its enzymatic activity. Collectively, these data demonstrate that Nampt participates in cellular resistance to genotoxic/oxidative stress, and it may confer to cells of the immune system the ability to survive during stressful situations such as inflammation. [less ▲]

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See detailUse of a human microarray to highlight new genes of interest for a better understanding of recurrent airway obstruction in horses (heaves)
Ramery, Eve ULg; Closset, R.; Bureau, Fabrice ULg et al

in XVIth International Plant & Animal Genome Conference (2008)

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See detailAnti-inflammatory effects of ipratropium bromide in rats with cadmium-induced acute pulmonary inflammation
Zhang, Yinghong ULg; Fievez, Laurence ULg; Cheu, Esteban ULg et al

in Fundamental & Clinical Pharmacology (2008), 22(1), 7

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See detailProlactin-induced activation of nuclear factor kappa B in bovine mammary epithelial cells: Role in chronic mastitis
Boutet, Philippe ULg; Sulon, Joseph ULg; Closset, R. et al

in Journal of Dairy Science (2007), 90(1), 155-164

We sought to determine whether prolactin (PRL) could influence the neutrophilic inflammation that characterizes chronic mastitis. Most of the genes encoding inflammatory proteins depend on the nuclear ... [more ▼]

We sought to determine whether prolactin (PRL) could influence the neutrophilic inflammation that characterizes chronic mastitis. Most of the genes encoding inflammatory proteins depend on the nuclear factor kappa B (NF-kappa B) for their expression. We addressed the hypothesis that immunomodulatory activities of PRL might arise from an increase in NF-kappa B activity. MAC-T cells, a bovine mammary epithelial cell line, were stimulated with increasing concentrations of bovine PRL ( 1, 5, 25, 125, and 1,000 ng/mL). Level of NF-kappa B binding activity was measured and mRNA was evaluated for IL-1 beta, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GMCSF), IFN-gamma, and tumor necrosis factor (TNF)-alpha, cytokines known to require NF-kappa B for their maximal transcription. Prolactin activated NF-kappa B; maximal NF-kappa B activation was weaker with PRL than with TNF-alpha at 30 or 180 min poststimulation. In addition, PRL significantly amplified, in a dose-dependent manner, mRNA expression of IL-1 beta, IL-6, IL-8, GMCSF, and TNF-a. We measured PRL concentrations in blood and milk from healthy and chronic mastitis-infected cows, and studied the relationship between the PRL concentration and the degree of inflammation in the mammary gland as indirectly assessed by somatic cell counts (SCC). Plasma PRL did not differ significantly between healthy and chronic mastitis-affected cows (63.7 and 67.5 ng/mL, respectively). Milk PRL concentration was significantly increased in chronic mastitis-affected quarters with the highest SCC, and had a positive significant correlation between SCC, as well as between the number of neutrophils present in milk samples. The present findings show that PRL promotes an inflammatory response in bovine mammary epithelial cells via NF-kappa B activation, and suggest a role for PRL in the pathogenesis of chronic mastitis. [less ▲]

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See detailPotential use of micro-array technology (bio-puce) in the diagnosis of inflammatory disorders in the horse
Lekeux, Pierre ULg; Thomas, A.; Ramery, Eve ULg et al

in XVII. Tagung über Pferdekrankheiten im Rahmen der EQUITANA (2007)

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See detailStat5 Is an Ambivalent Regulator of Neutrophil Homeostasis
Fievez, Laurence ULg; Desmet, Christophe ULg; Henry, Emmanuelle et al

in PLoS ONE (2007), 2(1), 727

Although STAT5 promotes survival of hematopoietic progenitors, STAT5-/- mice develop mild neutrophilia. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that in STAT5-/- mice, liver endothelial cells (LECs ... [more ▼]

Although STAT5 promotes survival of hematopoietic progenitors, STAT5-/- mice develop mild neutrophilia. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that in STAT5-/- mice, liver endothelial cells (LECs) autonomously secrete high amounts of G-CSF, allowing myeloid progenitors to overcompensate for their intrinsic survival defect. However, when injected with pro-inflammatory cytokines, mutant mice cannot further increase neutrophil production, display a severe deficiency in peripheral neutrophil survival, and are therefore unable to maintain neutrophil homeostasis. In wild-type mice, inflammatory stimulation induces rapid STAT5 degradation in LECs, G-CSF production by LECs and other cell types, and then sustained mobilization and expansion of long-lived neutrophils. CONCLUSION: We conclude that STAT5 is an ambivalent factor. In cells of the granulocytic lineage, it exerts an antiapoptotic function that is required for maintenance of neutrophil homeostasis, especially during the inflammatory response. In LECs, STAT5 negatively regulates granulopoiesis by directly or indirectly repressing G-CSF expression. Removal of this STAT5-imposed brake contributes to induction of emergency granulopoiesis. [less ▲]

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See detailAnti-inflammatory effects of formoterol in rats after a single dose inhalation of nebulized cadmium
Zhang, W. H.; Fievez, Laurence ULg; Cheu, Esteban ULg et al

in Fundamental & Clinical Pharmacology (2007), 74

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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 detailEffects of formoterol on repeated cadmium inhalation-induced lung inflammation and emphysema in rats
Zhang, W.; Fievez, Laurence ULg; Cheu, Esteban ULg et al

in Proceedings : Congrès de physiologie, de pharmacologie et de thérapeutique P2T (2007)

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See detailInvestigation of pulmonary expression of heat shock protein HSP70 in mice chronically exposed to cigarette smoke
Cheu, Esteban ULg; Steuve, J.; Fievez, Laurence ULg et al

in Proceedings: Autumn Meeting of the Belgian Society of Fundamental and Clinical Physiology and Pharmacology (2007)

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See detailInfluence of different exposure conditions to cigarette smoke on the pulmonary acute inflammatory response in mice
Steuve, J.; Cheu, Esteban ULg; Fievez, Laurence ULg et al

in Proceedings: Autumn Meeting of the Belgian Society of Fundamental and Clinical Physiology and Pharmacology (2007)

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