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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 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 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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See detailSTAT5 is an Ambivalent Regulator of Neutrophil Homeostasis
Fievez, Laurence ULg; Desmet, Christophe ULg; Henry, E. et al

Poster (2007)

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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, C. J.; Garzé, V. et al

Poster (2007)

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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.; Zhang, F.; 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 detailCaractériser un profil inflammatoire grâce à l'utilisation du microdamier
Ramery, Eve ULg; Closset, Rodrigue; Bureau, Fabrice ULg et al

Poster (2007)

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See detailHelenalin reduces Staphylococcus aureus infection in vitro and in vivo
Boulanger, D.; Brouillette, E.; Jaspar, F. et al

in Veterinary Microbiology (2007), 119(2-4), 330-338

Staphylococcus (S.) aureus is a major udder pathogen causing bovine mastitis. Some pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), enhance extracellular and intracellular ... [more ▼]

Staphylococcus (S.) aureus is a major udder pathogen causing bovine mastitis. Some pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), enhance extracellular and intracellular growth of S. aureus, indicating that the inflammatory process favors S. aureus infection. Helenalin is a sesquiterpene lactone with potent anti-inflammatory properties. This study was designed to evaluate the effects of helenalin on S. aureus infection. First, in vitro experiments were conducted. These studies revealed that proliferation of S. aureus in bovine mammary epithelial MAC-T cells treated in the presence or absence of TNF-alpha was markedly reduced in the presence of helenalin. Secondly, in vivo effects of helenalin were investigated. Lactating mice treated in the presence or absence of helenalin were challenged by the intramammary route with S. aureus and the bacteria in the mammary glands were counted 12 h after infection. Significantly less numbers of bacteria were recovered from the infected glands of helenalin-treated mice compared with untreated mice. Moreover, histological examination of mammary tissue from helenalin-treated mice that were challenged with S. aureus indicated that helenalin is able to significantly reduce leukocyte infiltration in the mammary gland following S. aureus inoculation. Our results show that helenalin reduces S. aureus intracellular growth and experimental S. aureus infection. We conclude that helenalin may be of potential interest in the treatment of S. aureus-induced mastitis in the bovine species. [less ▲]

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See detailCysteinyl-leukotrienes contribute to sputum eosinophil chemotactic activity in asthmatics
Hemelaers, L.; Henket, Monique ULg; Sele, Jocelyne ULg et al

in Allergy (2006), 61(1), 136-139

Background: Cysteinyl-leukotrienes are lipid derived mediators involved in asthma. They are able to stimulate eosinophil chemotaxis in vitro. Induced sputum from asthmatics has been shown to contain ... [more ▼]

Background: Cysteinyl-leukotrienes are lipid derived mediators involved in asthma. They are able to stimulate eosinophil chemotaxis in vitro. Induced sputum from asthmatics has been shown to contain eosinophil chemotactic activity. The purpose of our study was to evaluate the contribution of cysteinyl-leukotrienes to sputum eosinophil chemotactic activity in asthmatics and to seek whether there might be differences between asthmatics free of inhaled corticosteroids vs those regularly receiving this treatment. Methods: Twenty-two patients (11 corticosteroid free, mean FEV1 99% predicted, 11 corticosteroid-treated, mean FEV1 77% predicted) recruited from our asthma clinic underwent a sputum induction. Sputum was processed according to standard procedure. Eosinophil chemotactic activity contained in the fluid phase was assessed using Boyden microchamber model and expressed as chemotaxis index (CI). Cysteinyl-leukotrienes were measured in sputum supernatant by ELISA and their role in sputum eosionophil chemotactic activity was evaluated by using montelukast, a selective antagonist of a cys-LT1 receptor. Results: Cysteinyl-leukotrienes were well detectable in sputum supernatants from both steroid-naive (247 +/- 42 pg/ml) and steroid-treated (228 +/- 26 pg/ml) asthmatics. Sputum eosinophil chemotactic activity was indiscriminately present in both corticosteroid-naive (CI: 2.61 +/- 0.22) and corticosteroid-treated (2.98 +/- 0.35) asthmatics. Montelukast (100 mu M) significantly inhibited the eosinophil chemotactic activity in both groups achieving a mean inhibition of 54.2 +/- 9.2% (P < 0.001) and 64.7 +/- 7.8% (P < 0.001) in steroid-naive and steroid-treated asthmatics respectively. Conclusion: Cysteinyl-leukotrienes actively participate in sputum eosinophil chemotactic activity found in asthmatics irrespective of whether they are or not under treatment with inhaled corticoids. [less ▲]

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See detailTableau clinique et mécanismes physiopathologiques des principales maladies inflammatoires chroniques des voies respiratoires du cheval
Mesnil, Claire ULg; Bureau, Fabrice ULg; Lekeux, Pierre ULg

in Annales de Médecine Vétérinaire (2006), 150(4), 227-240

The respiratory tract of the horse can be the seat of several chronic inflammatory diseases whose principal ones are the recurrent airway obstruction, the inflammatory airway disease, the summer pasture ... [more ▼]

The respiratory tract of the horse can be the seat of several chronic inflammatory diseases whose principal ones are the recurrent airway obstruction, the inflammatory airway disease, the summer pasture-associated obstructive pulmonary disease and the follicular pharyngitis. These diseases can have an important impact on horses’ health and on their sports performances. A good knowledge of their aetiologies and their physiopathological mechanisms would allow a better control of these affections. However, even if many studies were made on this subject, there are currently very few certainties as for the inflammatory mechanisms governing these diseases. This article aims to make an inventory of knowledge and deficiencies concerning these four chronic inflammatory diseases [less ▲]

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See detailInvasion intracellulaire des cellules non-phagocytaires par Staphylococcus aureus
Boulanger, Delphine; Bureau, Fabrice ULg; Lekeux, Pierre ULg

in Annales de Médecine Vétérinaire (2006), 150(1), 27-42

Intracellular invasion of Staphyloccocus aureus in nonphagocytic cells Staphylococcus aureus often causes chronic diseases. It is now believed that recurrence of these infections could be related to the ... [more ▼]

Intracellular invasion of Staphyloccocus aureus in nonphagocytic cells Staphylococcus aureus often causes chronic diseases. It is now believed that recurrence of these infections could be related to the ability of S. aureus to invade and persist within nonphagocytic cells. Adherence to eucaryotic cells is crucial for S. aureus to invade and persist within invasion and depends on interactions between bacterial fibronectin-binding proteins, fibronectin and the host cell fibronectin receptor, integrin alpha(5)beta(1). It is currently established that fibronectin acts as a bridging molecule. Penetration of S. aureus in host cells requires also activation of protein tyrosine kinases that mediate signal transduction and actin polymerization leading to cytoskeletal rearrangements. After internalization, S. aureus either remains in membrane-bound vacuoles or appears free in the cytoplasm. After bacterial proliferation, S. aureus induces host cell apoptosis or persist inside cells as small colony variants, which represent a less virulent subpopulation of S. aureus that grows slower. Although numerous in vitro and in vivo studies have demonstrated the ability of S. aureus to invade nonphagocytic cells, additional experiments have to be realized to understand the relevance of intracellular localization in vivo. [less ▲]

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See detailLa mammite bovine : de l’initiation à la résolution
Boutet, Philippe ULg; Bureau, Fabrice ULg; Lekeux, Pierre ULg

in Annales de Médecine Vétérinaire (2006), 150(1), 1-26

The bovine mastitis : from initiation to resolution The cure of a cow suffering from a bacterial mastitis relies on the balance between the eradication of the pathogen and the resolution of the ... [more ▼]

The bovine mastitis : from initiation to resolution The cure of a cow suffering from a bacterial mastitis relies on the balance between the eradication of the pathogen and the resolution of the inflammatory response, two processes that are essential to come back to a normal milk composition with low somatic cell count. The persistence of the inflammatory response, which main consequence is a reduction in milk yield, is a feature of chronic mastitis. This frequent disease depends on inappropriate host-pathogen interactions and is not yet well understood. This review resumes the main defence mechanisms of the bovine mammary gland, emphasizing the predominant roles played by the neutrophil, and brings some precisions on lipoxin implications in the resolution of inflammation. Reasons that may explain the persistence of the inflammatory reaction, a phenomenon found in the Staphylococcus aureus chronic mastitis, are also discussed. [less ▲]

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