References of "Lekeux, Pierre"
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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 (2015), 44(1), 37-46

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 detailThe Innate Immune Response of Equine Bronchial Epithelial Cells is Altered by Training
Frellstedt, Linda ULg; Gosset, Philippe; Kervoaze, Gwenola et al

in Veterinary Research (2015), 46(3), 1-12

Respiratory diseases, including inflammatory airway disease (IAD), viral and bacterial infections, are common problems in exercising horses. The airway epithelium constitutes a major physical barrier ... [more ▼]

Respiratory diseases, including inflammatory airway disease (IAD), viral and bacterial infections, are common problems in exercising horses. The airway epithelium constitutes a major physical barrier against airborne infections and plays an essential role in the lung innate immune response mainly through toll-like receptor (TLR) activation. The aim of this study was to develop a model for the culture of equine bronchial epithelial cells (EBEC) in vitro and to explore EBEC innate immune responses in trained horses. Bronchial epithelial biopsies were taken from 6 adult horses during lower airway endoscopy. EBEC were grown in vitro by an explant method. The innate immune response of EBEC was evaluated in vitro by treatment with TLR ligands. TLR3 is the most strongly expressed TLR at the mRNA level in EBEC and stimulation of EBEC with Poly(I:C), an analog of viral dsRNA, triggers a strong secretion of IFN-β, TNF-α, IL-6 and CXCL8. We further evaluated the EBEC innate immune response in horses that underwent a 4-month-training program. While training had no effect on TLR mRNA expression in EBEC as well as in bronchial biopsies, it increased the production of IFN-β after stimulation with a TLR3 ligand and decreased the secretion of TNF-α and IL-6 after stimulation with a TLR2 and TLR3 ligand. These findings may be implicated in the increased risk for viral and bacterial infections observed in sport horses. Altogether, we report a successful model for the culture of EBEC that can be applied to the investigation of pathophysiologic conditions in longitudinal studies. [less ▲]

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See detailStimulation of airway neutrophils following dexamethasone administration and equid herpesvirus-2 challenge in horses
Richard, Eric A.; Pitel, Pierre-Hugues; Lemaitre, Laurent et al

in Veterinary journal (London, England : 1997) (2014), 199(1), 181-183

The aim of this study was to investigate neutrophil stimulation following experimentally-induced airway inflammation in healthy horses. Six horses received dexamethasone and four were then inoculated with ... [more ▼]

The aim of this study was to investigate neutrophil stimulation following experimentally-induced airway inflammation in healthy horses. Six horses received dexamethasone and four were then inoculated with equid herpesvirus-2 (EHV-2). Significant neutrophilia was detected in tracheal wash and bronchoalveolar lavage fluid for up to 6 days. Concentrations of neutrophil elastase (NE) and myeloperoxidase (MPO) were significantly increased compared to baseline for up to 14 days in tracheal washes and both markers were significantly correlated with neutrophil counts. Serum levels of surfactant protein D were not significantly modified throughout the study. These results suggest that dexamethasone administration with or without EHV-2 inoculation is associated with a sustainable activation and degranulation of neutrophils in the trachea along with moderate modifications detectable in the lower airways. [less ▲]

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See detailTraining Modifies Innate Immune Responses in Blood Monocytes and in Pulmonary Alveolar Macrophages
Frellstedt, Linda ULg; Waldschmidt, Ingrid; Gosset, Philippe et al

in American Journal of Respiratory Cell and Molecular Biology (2014), 51(1), 135-142

In humans, strenuous exercise causes increased susceptibility to respiratory infections associated with down-regulated expression of Toll-like receptors (TLRs), co-stimulatory and antigen-presenting ... [more ▼]

In humans, strenuous exercise causes increased susceptibility to respiratory infections associated with down-regulated expression of Toll-like receptors (TLRs), co-stimulatory and antigen-presenting molecules. Lower airway diseases are also a common problem in sport and racing horses. Because the innate immunity plays an essential role in lung defense mechanisms, we aimed to assess the effect of acute exercise and training on innate immune responses in two different compartments. Blood monocytes and pulmonary alveolar macrophages (PAM) were collected from horses in an untrained, moderately and intensively trained as well as deconditioned state before and after a strenuous exercise test (SET). The cells were analysed for TLR mRNA expression by real-time PCR in vitro and the cytokine production after in vitro stimulation with TLR ligands was measured by ELISA. Our results showed that training, but not acute exercise, modified the innate immune responses in both compartments. The mRNA expression of TLR3 was down-regulated by training in both cell types, whereas the expression of TLR4 was up-regulated in monocytes. Monocytes treated with lipopolysaccharide (LPS) and a synthetic diacylated lipoprotein (FSL) showed increased cytokine secretion in trained and deconditioned subjects indicating the activation of cells at the systemic level. The production of TNF-alpha and IFN-beta in non-stimulated and stimulated PAM was decreased in trained and deconditioned horses and might therefore explain the increased susceptibility to respiratory infections. Our study reports a dissociation between the systemic and the lung response to training that is probably implicated in the systemic inflammation and in the pulmonary susceptibility to infection. [less ▲]

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See detailResident lung CD11b+Ly6C- 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 Proceeding of International Congress of Immunology 2013 (2013)

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See detailTraining modifies the innate immune response both in the airways and in blood in horses
Frellstedt, Linda ULg; Gosset, Philippe; Desmet, Christophe ULg et al

in Proceedings of the ICI (2013)

Lower airway diseases are common problems in sports and racing horses. In humans, exercise has been associated with upper respiratory tract infections due to down-regulated expression of Toll-like ... [more ▼]

Lower airway diseases are common problems in sports and racing horses. In humans, exercise has been associated with upper respiratory tract infections due to down-regulated expression of Toll-like receptors (TLRs), costimulatory and antigen-presenting molecules on monocytes. The objectives of this study were 1) to examine the expression of TLRs in equine bronchial epithelial cells (EBEC) and blood monocytes in untrained and trained horses; 2) to stimulate EBEC and monocytes in vitro with TLR ligands, in order to mimic bacterial/viral infections; 3) to compare the cytokine production of EBEC and monocytes in untrained and trained horses. Bronchial biopsies were taken from 8 horses during lower airway endoscopy at rest and 24 hours after a standardized exercise test (SET). Bronchial epithelial cells were grown in vitro and activated with TLR ligands. Blood monocytes were collected at rest and after the SET. TLR1-TLR9 expression was evaluated via real-time PCR and cytokine production was measured via ELISA. TLR3 and TLR4 expression was modified by training. The expression of TLR2, TLR7 and TLR8 was modified only by strenuous exercise in trained horses. Training had local immuno-suppressive effects shown by a decreased production of TNF-alpha and IFN-beta in EBEC in response to TLR2 and TLR3 ligands. Training also caused a systemic pro-inflammatory response evidenced by increased production of TNF-alpha in monocytes in response to TLR2 and TLR4 ligands. These findings suggest that training and strenuous exercise in trained subjects may result in an increased susceptibility of the lower airway to infections associated with systemic inflammation. [less ▲]

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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 detailDetection of copy number variants in the horse genome and examination of their association with recurrent laryngeal neuropathy
Dupuis, Marie-Capucine; Zhang, Zhiyan ULg; Durkin, Keith ULg et al

in Animal Genetics (2013)

We used the data from a recently performed genome-wide association study using the Illumina Equine SNP50 beadchip for the detection of copy number variants (CNVs) and examined their association with ... [more ▼]

We used the data from a recently performed genome-wide association study using the Illumina Equine SNP50 beadchip for the detection of copy number variants (CNVs) and examined their association with recurrent laryngeal neuropathy (RLN), an important equine upper airway disease compromising performance. A total of 2797 CNVs were detected for 477 horses, covering 229 kb and seven SNPs on average. Overlapping CNVs were merged to define 478 CNV regions (CNVRs). CNVRs, particularly deletions, were shown to be significantly depleted in genes. Fifty-two of the 67 common CNVRs (frequency ! 1%) were validated by association mapping, Mendelian inheritance, and/or Mendelian inconsistencies. None of the 67 common CNVRs were significantly associated with RLN when accounting for multiple testing. However, a duplication on chromosome 10 was detected in 10 cases (representing three breeds) and two unphenotyped parents but in none of the controls. The duplication was embedded in an 8-Mb haplotype shared across breeds. [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 detailThe respiratory system: anatomy, physiology, and adaptations to exercise and training
Lekeux, Pierre ULg; Art, Tatiana ULg; Hodgson, David R

in Hodgson, D.R.; McKeever, K.H.; McGowan, C.M. (Eds.) The Athletic Horse. Principles and Practice of Equine Sports Medicine Second Edition (2013)

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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 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)

Detailed reference viewed: 38 (14 ULg)
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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 detailMethacholine bronchoprovocation test:a useful ancillary test for diagnosis of hyperresponsiveness in horses ?
Frippiat, Thibault ULg; Frellstedt, Linda ULg; Bustin, Jean-Clément ULg et al

in Proceedings of the European Veterinary Conference - Voorjaarsdagen (2012)

Detailed reference viewed: 60 (2 ULg)