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See detailPrincipes des microdamiers à ADN et applications potentielles en sciences vétérinaires
Thomas, A.; Closset, Jean ULg; Bureau, Fabrice ULg et al

in Annales de Médecine Vétérinaire (2005), 149

Microarray technology is a miniaturized biotechnological tool with potential applications for study and analysis of multiple molecular compounds as proteins, lipids, carbohydrates or nucleic acids. The ... [more ▼]

Microarray technology is a miniaturized biotechnological tool with potential applications for study and analysis of multiple molecular compounds as proteins, lipids, carbohydrates or nucleic acids. The nucleic acids microarray technology focuses interest of scientists for fifteen years because of its huge potential as regard to the scientific research, clinical diagnosis, and development of new drugs. Only DNA microarrays are investigated in this paper. Born from the conjunction of micro-electronics, biochemistry, molecular biology, and image processing, microarrays allow to analyse several thousands of genetic information simultaneously. Thanks to this new tool, it is possible in parallel to identify, to even proportion, a considerable number of nucleic acid sequences contained in a biological sample (blood, biopsy, water, food, etc). This article proposes, after having considered the operating mode of the microarrays, to understand their quality standards as well as their advantages and disadvantages. The two following parts are devoted to the place the microarrays occupy in scientific research and in the establishment of a clinical diagnosis. Finally the last part evaluates prospects the microarrays offer in veterinary sciences. [less ▲]

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See detailLe controle de la transcription genique en tant que nouvelle cible therapeutique dans le traitement de l'asthme
Desmet, Christophe ULg; Louis, Renaud ULg; Lekeux, Pierre ULg et al

in Revue Médicale de Liège (2005), 60(10), 789-795

The recent advances in the knowledge of the molecular mechanisms underlying asthma have lead to a significant improvement of the current treatments of the disease and opened new perspectives for the ... [more ▼]

The recent advances in the knowledge of the molecular mechanisms underlying asthma have lead to a significant improvement of the current treatments of the disease and opened new perspectives for the development of therapeutic alternatives to inhaled corticosteroids. The selective targeting of transcription factors controlling the expression of the genes implicated in the pathogenesis of asthma is one of these privileged strategies. This review aims at describing the most promising new therapeutic targets in the control of asthmatic inflammation at the gene transcription level. [less ▲]

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See detailProstaglandin D2 affects the differentiation and functions of human dendritic cells: impact on the T cell response.
Gosset, Philippe; Pichavant, Muriel; Faveeuw, Christelle et al

in European Journal of Immunology (2005), 35(5), 1491-1500

The local environment in which dendritic cells (DC) differentiate is important for the acquisition of their immunostimulatory properties. Since prostaglandin D(2) (PGD(2)), a major prostanoid produced ... [more ▼]

The local environment in which dendritic cells (DC) differentiate is important for the acquisition of their immunostimulatory properties. Since prostaglandin D(2) (PGD(2)), a major prostanoid produced during inflammatory reactions, is involved in the control of immune responses, its effect on the differentiation and functions of human monocyte-derived dendritic cells (MDDC) was studied. We show that DC differentiated in the presence of PGD(2) (PG/DC) have an unusual phenotype, with modifications in the expression of molecules involved in antigen (Ag) capture and presentation, leading to higher endocytic and Ag-processing activities. However, under conditions that necessitated Ag processing and presentation, PG/DC have an impaired ability to stimulate naive T cells, whereas superAg-pulsed DC efficiently promote their proliferation. Upon lipopolysaccharide or TNF-alpha/IL-1beta stimulation, PG/DC phenotypically mature but produce abnormal amounts of immunoregulatory cytokines (decreased IL-12p70/IL-10 ratio). Moreover, mature PG/DC fail to up-regulate the chemokine receptor CCR7 and show an impaired migration towards its ligand CCL19. Finally, PG/DC favor the differentiation of naive T cells toward Th2 cells, an effect dependent on IL-10 and inducible costimulator ligand expression by DC. Most of the herein described effects of PGD(2) on MDDC can be reproduced, usually with a higher efficacy, with a selective D prostanoid receptor (DP)1, but not DP2, agonist. Taken as a whole, these results demonstrate that PGD(2) impacts DC differentiation and functions, and extend the concept that it exerts important roles in immunity [less ▲]

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See detailPro-inflammatory properties for thiazolidinediones.
Desmet, Christophe ULg; Warzée, Barbara ULg; Gosset, Philippe et al

in Biochemical Pharmacology (2005), 69(2), 255-265

Thiazolidinediones (TZDs) are pharmacological ligands of the peroxisome proliferator-activated receptor (PPAR)-gamma that are extensively used in the treatment of type II diabetes. Recently, an anti ... [more ▼]

Thiazolidinediones (TZDs) are pharmacological ligands of the peroxisome proliferator-activated receptor (PPAR)-gamma that are extensively used in the treatment of type II diabetes. Recently, an anti-inflammatory potential for TZDs has been suggested, based on observations that these compounds may inhibit pro-inflammatory cytokine expression in vitro and may attenuate the inflammatory response in vivo. Here, we show that the TZDs rosiglitazone (RSG) and troglitazone (TRO) do not inhibit the inflammatory response to tumor necrosis factor (TNF)-alpha in various epithelial cell types. On the contrary, both RSG and TRO significantly potentiated TNF-alpha-induced production of granulocyte/macrophage-colony-stimulating factor, interleukin (IL)-6 and/or IL-8 in these cells. This increase in pro-inflammatory cytokine expression was functionally significant as supernatants from cells co-treated with TNF-alpha and TZDs displayed increased neutrophil pro-survival activity when compared with supernatants from cells treated with TNF-alpha alone. Additionally, it was shown that TZDs enhance cytokine expression at the transcriptional level, but that the pro-inflammatory effects of TZDs are independent on PPARgamma, nuclear factor kappaB or mitogen-activated protein kinase activation. Our study shows that TZDs may potentiate the inflammatory response in epithelial cells, a previously unappreciated effect of these compounds [less ▲]

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See detailSTAT5 promotes granulocyte survival during inflammation
Fievez, Laurence ULg; Desmet, Christophe ULg; Seumois, G. et al

in Proceedings: The American Thoracic Society (2005)

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See detailSelective inhibition of AP-1 activity in airway immune cells ameliorates experimental asthma
Desmet, Christophe ULg; Gosset, P.; Garzé, V. et al

in Proceedings: The American Thoracic Society (2005)

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See detailTreatment of experimental asthma by decoy-mediated local inhibition of activator protein-1
Desmet, Christophe ULg; Gosset, P.; Henry, E. et al

in American Journal of Respiratory & Critical Care Medicine (2005), 172(6), 671-678

Rationale: Asthma is associated with increased expression of a typical array of genes involved in immune and inflammatory responses, including those encoding the prototypic Th2 cytokines interleukin (IL ... [more ▼]

Rationale: Asthma is associated with increased expression of a typical array of genes involved in immune and inflammatory responses, including those encoding the prototypic Th2 cytokines interleukin (IL) 4, IL-5, and IL-13. Most of these genes contain binding sites for activator protein-1 (AP-1) within their promoter and are therefore believed to depend on AP-1 for their expression, suggesting that this transcription factor could be of particular importance in asthma pathophysiology. Objective: To clarify the role of AP-1 in the effector phase of pulmonary allergy. Methods: Ovalbumin (OVA)-sensitized mice were intratracheally given decoy oligodeoxyribonucleotides (ODNs) specifically directed to AP-1 or scrambled control ODNs before challenge with aerosolized OVA. Twenty-four hours after the last OVA challenge, airway hyperresponsiveness was measured and allergic airway inflammation was evaluated quantitatively. AP-1 decoys were localized using flow cytometry and immunohistochemistry. AP-1 activity in the lung was assessed using electrophoretic mobility shift assay. Measurements and Main Results: Intratracheally delivered AP-1 decoys efficiently targeted airway immune cells, thus precluding AP-1 activation on OVA challenge. Decoy-mediated local inhibition of AP-1 resulted in significant attenuation of all the pathophysiologic features of experimental asthma-namely, eosinophilic airway inflammation, airway hyperresponsiveness, mucous cell hyperplasia, production of allergen-specific immunoglobulins, and synthesis of IL-4, IL-5, and IL-13. Scrambled control ODNs had no detectable effects. Conclusions: Our results reveal a key role for AP-1 in the effector phase of pulmonary allergy and indicate that specific AP-1 inhibition in the airways may have therapeutic value in the control of established asthma. [less ▲]

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See detailNouvelles approches du traitement des affections respiratoires du bétail
Lekeux, Pierre ULg; Bureau, Fabrice ULg

in Point Vétérinaire (2005), 252

Devant des affections surtout polyfactorielles, l’ère du “tout antibiotique” semble révolue, comme l’illustrent certaines pistes actuelles de recherche.

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See detailSelective decoy-mediated inhibition of activator protein-1 activity in the airways pevents experimental asthmatic inflammation
Desmet, Christophe ULg; Gosset, P.; Pajak, B. et al

in European Respiratory Journal (2005), 26

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See detailGSK3-Mediated BCL-3 phosphorylation modulates its degradation and its oncogenicity
Viatour, Patrick ULg; Dejardin, Emmanuel ULg; Warnier, Michael et al

in Molecular Cell (2004), 16(1), 35-45

The oncoprotein BCL-3 is a nuclear transcription factor that activates NF-kappaB target genes through formation of heterocomplexes with p50 or p52. BCL-3 is phosphorylated in vivo, but specific BCL-3 ... [more ▼]

The oncoprotein BCL-3 is a nuclear transcription factor that activates NF-kappaB target genes through formation of heterocomplexes with p50 or p52. BCL-3 is phosphorylated in vivo, but specific BCL-3 kinases have not been identified so far. In this report, we show that BCL-3 is a substrate for the protein kinase GSK3 and that GSK3-mediated BCL-3 phosphorylation, which is inhibited by Akt activation, targets its degradation through the proteasome pathway. This phosphorylation modulates its association with HDAC1, -3, and -6 and attenuates its oncogenicity by selectively controlling the expression of a subset of newly identified target genes such as SLPI and CxcI1. Our results therefore suggest that constitutive BCL-3 phosphorylation by GSK3 regulates BCL-3 turnover and transcriptional activity. [less ▲]

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See detailCeramides play a critical role in spontaneous neutrophil apoptosis
Seumois, G.; Fillet, Marianne ULg; Gillet, Laurent ULg et al

in Pflügers Archiv : European Journal of Physiology (2004), 447

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See detailActivator protein-1 activity in bronchial brushing samples from horses with recurrent airway obstruction
Couëtil, L.; Art, Tatiana ULg; Bureau, Fabrice ULg et al

in Proceedings of the 22nd Symposium of the Veterinary and Comparative Respiratory Society (2004)

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See detailNuclear factor kappaB inhibition in bovine mammary epithelial cells reduces intracellular infection by Staphylococcus aureus.
Boulanger, D.; Bureau, Fabrice ULg; Lekeux, Pierre ULg

in Proceedings : 23rd World Buiatrics Congress (2004)

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See detailSTAT5 promotes granulocyte survival during inflammation
Fievez, Laurence ULg; Desmet, Christophe ULg; Pajak, B. et al

in Pflügers Archiv : European Journal of Physiology (2004), 447

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See detailEffects of thiazolidinediones on tumor necrosis factor R alpha induced inflammatory cytokine expression
Desmet, Christophe ULg; Warsée, Barbara; Mélotte, D. et al

in Pflügers Archiv : European Journal of Physiology (2004), 447

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See detailEvidence for a role of heat shock factor 1 in inhibition of NF-kB pathway during heat shock response-mediated lung protection
Wirth, D.; Bureau, Fabrice ULg; Melotte, D. et al

in American Journal of Physiology - Lung Cellular and Molecular Physiology (2004), 287

Heat shock transcription factor (HSF)-1 is recognized as a central component of the heat shock response, which protects against various harmful conditions. However, the mechanisms underlying the ... [more ▼]

Heat shock transcription factor (HSF)-1 is recognized as a central component of the heat shock response, which protects against various harmful conditions. However, the mechanisms underlying the protection and the role of HSF-1 in these mechanisms have not yet been clearly elucidated. Using HSF-1 knockout mice (Hsf1_/_), we examined whether heat shock responsemediated lung protection involved an inhibition of the proinflammatory pathway via an interaction between HSF-1 and NF-_B, in response to cadmium insult. The HSF-1-dependent protective effect against intranasal instillation of cadmium (10 and 100 _g/mouse) was demonstrated by the higher protein content (1.2- and 1.4-fold), macrophage (1.6- and 1.9-fold), and neutrophil (2.6- and 1.8-fold) number in bronchoalveolar fluids, higher lung wet-to-dry weight ratio, and more severe lung damage evaluated by histopathology in Hsf1_/_compared with wild-type animals. These responses were associated with higher granulocyte/macrophage colony-stimulating factor (GMCSF; 1.7-fold) but not TNF-_ concentrations in bronchoalveolar fluids of Hsf1_/_ mice compared with those of wild-type animals, indicating that HSF-1 behaved as a repressor of specific cytokine production in our model. To further investigate the mechanism of GM-CSF repression, we analyzed the NF-_B activity and I_B stability. The DNA binding NF-_B activity, in particular p50 homodimer activity, was higher in Hsf1_/_ mice than in wild-type mice after cadmium exposure. These results provide a first line of evidence that mechanisms of lung protection depending on HSF-1 involve specific cytokine repression via inhibition of NF-_B activation in vivo. [less ▲]

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See detailChronic mastitis-affected cows display lower lipoxin levels than acute mastitis-affected cows
Boutet, Philippe ULg; Bureau, Fabrice ULg; Degand, Guy ULg et al

in Pflügers Archiv : European Journal of Physiology (2004), 447

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See detailDelayed neutrophil apoptosis in bovine subclinical mastitis.
Boutet, Philippe ULg; Boulanger, D.; Gillet, Laurent ULg et al

in Journal of Dairy Science (2004), 87(12), 4104-4114

Bovine subclinical mastitis can be defined as a moderated inflammatory disease characterized by a persistent accumulation of neutrophils in milk. As GMCSF-mediated delay of neutrophil apoptosis ... [more ▼]

Bovine subclinical mastitis can be defined as a moderated inflammatory disease characterized by a persistent accumulation of neutrophils in milk. As GMCSF-mediated delay of neutrophil apoptosis contributes to the accumulation of inflammatory cells at the site of inflammation in many human diseases, we sought to determine whether subclinical mastitis in cows is also associated with a GMCSF-dependent increase in milk-neutrophil survival. We first addressed the hypothesis that GMCSF delays bovine neutrophil apoptosis by activation of the signal transducer and activator of transcription (STAT) family members STAT3 and STAT5, which are critical regulators of the expression of various Bcl-2 family proteins. Granulocyte-macrophage colony-stimulating factor significantly delayed apoptosis of blood neutrophils obtained from healthy cows. In these cells, GMCSF activated STAT5, but not STAT3, and induced an increase in the mRNA of the antiapoptotic Bcl-2 member, Bcl-xL. Granulocyte-macrophage colony-stimulating factor-dependent STAT5 activation and up-regulation of Bcl-xL mRNA were blocked by the Jak inhibitor, AG-490. This inhibition was associated with abrogation of the prosurvival effect of GMCSF, demonstrating a key role for STAT5 in delayed neutrophil apoptosis. We further found that GMCSF expression was increased in milk cells from cows affected with subclinical mastitis. Neutrophils from these cows demonstrated a significant delay of apoptosis as compared with neutrophils obtained from healthy cows and were unresponsive to GMCSF. Active STAT5 complexes were detected in these neutrophils. Finally, in the presence of AG-490, apoptosis was induced and a time-dependent down-regulation of Bcl-xL mRNA was observed in milk neutrophils from mastitis-affected cows. These results indicate that neutrophil survival is enhanced in milk of subclinical mastitis-affected cows and suggest a role for a GMCSF-activated STAT5 signaling pathway in this phenomenon. This pathway could thus represent a target for the control of persistent accumulation of neutrophils in the bovine mammary gland [less ▲]

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