References of "Bureau, Fabrice"
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See detailExpression microarray as a tool to identify candidate blood biomarkers in horses suffering from inflammatory airway disease
Ramery, Eve ULg; Fraipont, Audrey ULg; Art, Tatiana ULg et al

in Veterinary Clinical Pathology (in press)

Background: Inflammatory airway disease (IAD) affects performance and well-being in horses. Diagnosis is primarily reached by bronchoalveolar lavage (BAL) cytology but this is invasive and requires ... [more ▼]

Background: Inflammatory airway disease (IAD) affects performance and well-being in horses. Diagnosis is primarily reached by bronchoalveolar lavage (BAL) cytology but this is invasive and requires sedation. Objectives: The purpose of this study was to identify candidate blood biomarkers of IAD using species-specific expression microarrays. Methods: Horse Gene Expression Microarrays were used to investigate global mRNA expression in circulating leukocytes from healthy and IAD-affected standardbreds and endurance horses. Results: Nine genes were significantly differentially regulated in standardbreds and 61 in endurance horses (P < 0.001). These genes were mainly related to inflammation (eg. ALOX15B, PLA2G12B and PENK), oxidant/antioxidant balance (eg. DUOXA2 and GSTO1-1) and stress (eg. V1aR, GRLF1, Homer-2 and MAOB). DUOXA2, ALOX15B, PLA2G12B, MAOB and GRLF1 variations of expression were further validated by RT-qPCR. The deregulation of the oxidant/antioxidant balance was demonstrated at the protein level by an increase of glutathione peroxidase (GPx) activity in heparinised whole blood of IAD-affected standardbreds (P = 0.0025) and endurance horses (P = 0.0028). There was good correlation (r = 0.7354) between BAL neutrophil percentage and whole blood GPx activity in all horses. Conclusions: There is accumulating evidence that, even when systemic clinical signs are not evident, circulating leukocyte gene expression can reflect responses of other tissues, leading to potential diagnostic applications in the future. Although not specific for IAD, whole blood GPx activity appears to reflect BAL neutrophil percentage. This finding should be further assessed by testing a larger number of horses. [less ▲]

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See detailAnalysis of gene expression in canine idiopathic pulmonary fibrosis
Krafft, Emilie ULg; Laurila, HP; peters, IR et al

in Veterinary Journal (2013)

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See detailExercise modifies the innate immune response in equine bronchial epithelial cells
Frellstedt, Linda ULg; Gosset, Philippe; Pirottin, Dimitri ULg et al

in Proceedings of the 3rd Scientific Meeting of the Faculty of Veterinary Medicine (University of Liege - Belgium) (2013)

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See detailExperimental model of equine alveolar macrophage stimulation with TLR ligands.
Waldschmidt, Ingrid; Pirottin, Dimitri ULg; Art, Tatiana ULg et al

in Veterinary Immunology and Immunopathology (2013), 155(1-2), 30-37

Pulmonary diseases are common in horses and have a major economic impact on the equine industry. Some of them could be associated with an inadequate immune response in the lung, but methods to evaluate ... [more ▼]

Pulmonary diseases are common in horses and have a major economic impact on the equine industry. Some of them could be associated with an inadequate immune response in the lung, but methods to evaluate this response in horses are lacking. The aim of this study was to develop and validate an experimental model that could be applied in several physiological and pathological conditions to assess the innate immune response of equine pulmonary cells. Equine alveolar macrophages (AMs) obtained from bronchoalveolar lavages were isolated from other cells by adhesion. TLR2, 3, and 4 expression in AMs was studied and their responses to commercial ligands (respectively FSL-1, Poly(I:C), and LPS) were evaluated after determination of the appropriate dose and time of incubation. TLR responses were assessed by measuring cytokine production using (1) gene expression of TNFalpha, IFNbeta, Il-1beta, and IFNalpha by qPCR (indirect method); and (2) cytokine production for TNFalpha and IFNbeta by ELISA (direct method). TLR 2, 3, and 4 were expressed by AMs. TLR 2 stimulation with 10ng/mL of FSL-1 during 3h significantly increased IL-1beta and TNFalpha gene expression. TLR 3 stimulation with 1000ng/mL of Poly(I:C) during 1h increased IFNbeta, IFNalpha, Il-1beta and TNFalpha expression. TLR 4 stimulation with 100ng/mL of LPS during 3h increased TNFalpha, IFNbeta, and Il-1beta expression. Results obtained by ELISA quantification of TNFalpha and IFNbeta produced by AMs following stimulation during 6h were similar: FSL-1 increased TNFalpha production but not IFNbeta, Poly(I:C) and LPS increased production of IFNbeta and TNFalpha. In conclusion, pulmonary innate immunity of horses can be assessed ex vivo by measuring cytokine production following stimulation of AMs with TLR agonists. This experimental model could be applied under several conditions especially to improve the understanding of equine respiratory disease pathogenesis, and to suggest novel therapeutic opportunities. [less ▲]

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See detailMyeloid Hif1alpha counteracts allergic airway sensitization in mice through macrophage-mediated immunoregulation
Toussaint, Marie ULg; Fievez, Laurence ULg; Drion, Pierre ULg et al

in Abstract book of Keystone Symposium "Myeloid Cells: Regulation and Inflammation" (2013)

Hypoxia Inducible Factor (HIF) has important roles in promoting pro-inflammatory and bactericidal functions in myeloid cells. Conditional genetic ablation of its major subunit Hif1alpha in the myeloid ... [more ▼]

Hypoxia Inducible Factor (HIF) has important roles in promoting pro-inflammatory and bactericidal functions in myeloid cells. Conditional genetic ablation of its major subunit Hif1alpha in the myeloid lineage consequently results in decreased inflammatory responses in classical models of acute inflammation in mice. In contrast, we observed that mice conditionally deficient for Hif1alpha in myeloid cells display enhanced sensitivity to the development of airway allergy to the experimental allergen ovalbumin as well as to house dust mite antigens. Following allergen exposure, these mice indeed developed enhanced allergen-specific T cell responses due to augmented activation of lung dendritic cells. Further analyses supported the idea that upon allergen exposure, MyD88-dependent upregulation of Hif1alpha boosts the expression of the immunosuppressive cytokine Interleukin (IL)-10 by lung interstitial macrophages. Interstitial macrophage-derived IL-10 in turn counteracts allergen-induced lung dendritic cell activation, consequently preventing the development of allergen-specific T cell responses. Thus, this study supports that, in addition to its known pro-inflammatory activities, myeloid Hif1alpha possesses immunoregulatory functions implicated in the prevention of airway allergy. [less ▲]

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See detailMyeloid hypoxia-inducible factor 1alpha prevents airway allergy in mice through macrophage-mediated immunoregulation
Toussaint, Marie ULg; Fievez, Laurence ULg; Drion, Pierre ULg et al

in Mucosal Immunology (2013), 6(3), 485-97

Hypoxia-inducible factor (HIF) has important roles in promoting pro-inflammatory and bactericidal functions in myeloid cells. Conditional genetic ablation of its major subunit Hif1alpha in the myeloid ... [more ▼]

Hypoxia-inducible factor (HIF) has important roles in promoting pro-inflammatory and bactericidal functions in myeloid cells. Conditional genetic ablation of its major subunit Hif1alpha in the myeloid lineage consequently results in decreased inflammatory responses in classical models of acute inflammation in mice. By contrast, we report here that mice conditionally deficient for Hif1alpha in myeloid cells display enhanced sensitivity to the development of airway allergy to experimental allergens and house-dust mite antigens. We support that upon allergen exposure, MyD88-dependent upregulation of Hif1alpha boosts the expression of the immunosuppressive cytokine interleukin (IL)-10 by lung interstitial macrophages (IMs). Hif1alpha-dependent IL-10 secretion is required for IMs to block allergen-induced dendritic cell activation and consequently for preventing the development of allergen-specific T-helper cell responses upon allergen exposure. Thus, this study supports that, in addition to its known pro-inflammatory activities, myeloid Hif1alpha possesses immunoregulatory functions implicated in the prevention of airway allergy. [less ▲]

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See detailTraining-induced decrease of cytokines production by equine alveolar macrophages
Waldschmidt, Ingrid ULg; Frellstedt, Linda ULg; Art, Tatiana ULg et al

in Proceedings of the 6th Congress of the European College of Equine Internal Medicine (ECEIM) (2013)

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See detailMeasurement of serum albumin by protein electrophoresis and bromocresol green methods in canine and equine patients
Ramery, Eve ULg; Bureau, Fabrice ULg

in Veterinary Clinical Pathology (2012, December), 41(4), 5

Background: Bromocresol green method (BCG) is routinely used in veterinary laboratories to measure albumin. A good agreement between BCG and electrophoresis (SPE) in healthy domestic animals is reported ... [more ▼]

Background: Bromocresol green method (BCG) is routinely used in veterinary laboratories to measure albumin. A good agreement between BCG and electrophoresis (SPE) in healthy domestic animals is reported. However, in human medicine, at low albumin and high globulin concentrations, BCG also binds to α- and β-globulins fractions. Surprisingly, there is no recent literature evaluating the BCG method in diseased domestic animals. Objective: The purpose of the present study was therefore to compare the serum albumin values obtained by SPE and BCG in canine and equine patients. Methods: Albumin measured by BCG and SPE was compared in the serum from 30 canine and 30 equine patients. Results: Good correlation was found (Spearman´s rho rs = 0.91 in dogs and 0.84 in horses). However, Altman and Bland analysis of results showed a positive bias of BCG with SPE (3.41 g/l in horses and 0.41 g/l in dogs) that increased when only hypoalbuminemic patients were considered (4.17 g/l in horses and 1.31 g/l in dogs). Conclusion: Results confirm that, despite good correlation, BCG method tends to overestimate albumin, especially in hypoalbuminemic patients. This is particularly evident in horses. [less ▲]

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See detailInvestigation of the effect of exercise on the innate immunity in horses
Frellstedt, Linda ULg; Gosset, Philippe; Desmet, Christophe ULg et al

Poster (2012, October 19)

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See detailRelease and Innate detection of host cell DNA mediates the adjuvant effects of aluminum salts on adaptive responses
Marichal, Thomas ULg; Ohata, Keichii; Bedoret, Denis et al

in Proceedings of the 1St Winter School Immunology (2012, January)

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See detailL'ADN du soi, allie du systeme immunitaire pour la fonction adjuvante de l'alun
Marichal, Thomas ULg; Bureau, Fabrice ULg; Desmet, Christophe ULg

in Medecine Sciences : M/S (2012), 28(1), 31-3

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See detailResident CD11b(+)Ly6C(-) Lung Dendritic Cells Are Responsible for Allergic Airway Sensitization to House Dust Mite in Mice.
Mesnil, Claire ULg; Sabatel, Catherine ULg; Marichal, Thomas ULg et al

in PLoS ONE (2012), 7(12), 53242

Conventional dendritic cells (DCs) are considered to be the prime initiators of airway allergy. Yet, it remains unclear whether specific DC subsets are preferentially involved in allergic airway ... [more ▼]

Conventional dendritic cells (DCs) are considered to be the prime initiators of airway allergy. Yet, it remains unclear whether specific DC subsets are preferentially involved in allergic airway sensitization. Here, we systematically assessed the respective pro-allergic potential of individually sorted lung DC subsets isolated from house dust mite antigen (HDM)-treated donor mice, following transfer to naive recipients. Transfer of lung CD11c(+)CD11b(+) DCs, but not CD11c(+)CD11b(-)CD103(+) DCs, was sufficient to prime airway allergy. The CD11c(+)CD11b(+) DC subpopulation was composed of CD11c(+)CD11b(+)Ly6C(+) inflammatory monocyte-derived cells, whose numbers increase in the lungs following HDM exposure, and of CD11c(+)CD11b(+)Ly6C(-) DCs, which remain stable. Counterintuitively, only CD11c(+)CD11b(+)Ly6C(-) DCs, and not CD11c(+)CD11b(+)Ly6C(+) DCs, were able to convey antigen to the lymph nodes and induce adaptive T cell responses and subsequent airway allergy. Our results thus support that lung resident non-inflammatory CD11c(+)CD11b(+)Ly6C(-) DCs are the essential inducers of allergic airway sensitization to the common aeroallergen HDM in mice. [less ▲]

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See detailControl of Allergen-Induced Inflammation and Hyperresponsiveness by the Metalloproteinase ADAMTS-12
Paulissen, Geneviève ULg; El Hour, Mehdi; Rocks, Natacha ULg et al

in Journal of Immunology (2012), 189

A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) constitute a family of endopeptidases related to matrix metalloproteinases. These proteinases have been largely implicated in tissue ... [more ▼]

A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) constitute a family of endopeptidases related to matrix metalloproteinases. These proteinases have been largely implicated in tissue remodeling associated with pathological processes. Among them, ADAMTS12 was identified as an asthma-associated gene in a human genome screening program. However, its functional implication in asthma is not yet documented. The present study aims at investigating potential ADAMTS-12 functions in experimental models of allergic airways disease. Two different in vivo protocols of allergen-induced airways disease were applied to the recently generated Adamts12-deficient mice and corresponding wild-type mice. In this study, we provide evidence for a protective effect of ADAMTS-12 against bronchial inflammation and hyperresponsiveness. In the absence of Adamts12, challenge with different allergens (OVA and house dust mite) led to exacerbated eosinophilic inflammation in the bronchoalveolar lavage fluid and in lung tissue, along with airway dysfunction assessed by increased airway responsiveness following methacholine exposure. Furthermore, mast cell counts and ST2 receptor and IL-33 levels were higher in the lungs of allergen-challenged Adamts12-deficient mice. The present study provides, to our knowledge, the first experimental evidence for a contribution of ADAMTS-12 as a key mediator in airways disease, interfering with immunological processes leading to inflammation and airway hyperresponsiveness. [less ▲]

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See detailCan beta2-adrenoceptor agonists, anticholinergic drugs, and theophylline contribute to the control of pulmonary inflammation and emphysema in COPD?
Zhang, Wen-Hui; Zhang, Yong; Cui, Yong-Yao et al

in Fundamental & Clinical Pharmacology (2012), 26(1), 118-134

Chronic obstructive pulmonary disease (COPD) has become a global epidemic disease with an increased morbidity and mortality in the world. Inflammatory process progresses and contributes to irreversible ... [more ▼]

Chronic obstructive pulmonary disease (COPD) has become a global epidemic disease with an increased morbidity and mortality in the world. Inflammatory process progresses and contributes to irreversible airflow limitation. However, there is no available therapy to better control the inflammatory progression and therefore to reduce the exacerbations and mortality. Thus, the development of efficient anti-inflammatory therapies is a priority for patients with COPD. beta(2) -Adrenoceptor agonists and anticholinergic agents are widely used as first line drugs in management of COPD because of their efficient bronchodilator properties. At present, many studies in vitro and some data obtained in laboratory animals reveal the potential anti-inflammatory effects of these bronchodilators but their protective role against chronic inflammation and the development of emphysema in patients with COPD remains to be investigated. The anti-inflammatory effects of theophylline at low doses have also been identified. Beneficial interactions between glucocorticoids and bronchodilators have been reported, and signaling pathways explaining these synergistic effects begin to be understood, especially for theophylline. Recent data demonstrating interactions between anticholinergics with beta(2) -adrenoceptor agonists aiming to better control the pulmonary inflammation and the development of emphysema in animal models of COPD justify the priority to investigate the interactive effects of a tritherapy associating corticoids with the two main categories of bronchodilators. [less ▲]

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See detailSirtuin inhibition attenuates the production of inflammatory cytokines in lipopolysaccharide-stimulated macrophages.
Fernandes, Claudia A.; Fievez, Laurence ULg; Neyrinck, Audrey M. et al

in Biochemical and Biophysical Research Communications (2012), 420(4), 857-861

In several inflammatory conditions such as rheumatoid arthritis or sepsis, the regulatory mechanisms of inflammation are inefficient and the excessive inflammatory response leads to damage to the host ... [more ▼]

In several inflammatory conditions such as rheumatoid arthritis or sepsis, the regulatory mechanisms of inflammation are inefficient and the excessive inflammatory response leads to damage to the host. Sirtuins are class III histone deacetylases that modulate the activity of several transcription factors that are implicated in immune responses. In this study, we evaluated the impact of sirtuin inhibition on the activation of lipopolysaccharide (LPS)-stimulated J774 macrophages by assessing the production of inflammatory cytokines. The pharmacologic inhibition of sirtuins decreased the production of tumour necrosis factor-alpha (TNF-alpha) interleukin 6 (IL-6) and Rantes. The reduction of cytokine production was associated with decreased nuclear factor kappa B (NF-kappaB) activity and inhibitor kappa B alpha (IkappaBalpha) phosphorylation while no impact was observed on the phosphorylation status of p38 mitogen-activated kinase (p38 MAPK). This work shows that sirtuin pharmacologic inhibitors are a promising tool for the treatment of inflammatory conditions. [less ▲]

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See detailIncreased hypoxia-inducible factor 1alpha expression in lung cells of horses with recurrent airway obstruction.
Toussaint, Marie ULg; Fievez, Laurence ULg; Desmet, Christophe ULg et al

in BMC Veterinary Research (2012), 8(1), 64

ABSTRACT: BACKGROUND: Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological ... [more ▼]

ABSTRACT: BACKGROUND: Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological processes responsible for the development and the persistence of airway inflammation are still largely unknown. Hypoxia-inducible factor (Hif) is mainly known as a major regulator of energy homeostasis and cellular adaptation to hypoxia. More recently however, Hif also emerged as an essential regulator of innate immune responses. Here, we aimed at investigating the potential involvement of Hif1-alpha in myeloid cells in horse with recurrent airway obstruction. RESULTS: In vitro, we observed that Hif is expressed in equine myeloid cells after hay dust stimulation and regulates genes such as tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGF-A). We further showed in vivo that airway challenge with hay dust upregulated Hif1-alpha mRNA expression in myeloid cells from the bronchoalveolar lavage fluid (BALF) of healthy and RAO-affected horses, with a more pronounced effect in cells from RAO-affected horses. Finally, Hif1-alpha mRNA expression in BALF cells from challenged horses correlated positively with lung dysfunction. CONCLUSION: Taken together, our results suggest an important role for Hif1-alpha in myeloid cells during hay dust-induced inflammation in horses with RAO. We therefore propose that future research aiming at functional inactivation of Hif1 in lung myeloid cells could open new therapeutic perspectives for RAO. [less ▲]

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