References of "Fievez, Laurence"
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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 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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See detailMyeloid HIF-1alpha prevents airway allergy in mice by promoting macrophage-mediated immunosuppression
Toussaint, Marie ULg; Fievez, Laurence ULg; Lekeux, Pierre ULg et al

in Proceedings of the 1st Scientific Meeting of the Faculty of Veterinary Medicine (2011, December 09)

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See detailSirtuin 1 Promotes Th2 Responses and Airway Allergy by Repressing Peroxisome Proliferator-Activated Receptor-γ Activity in Dendritic Cells
Legutko, Agnieszka; Marichal, Thomas ULg; Fievez, Laurence ULg et al

in Journal of Immunology (2011), 187(9), 4517-4529

Sirtuins are a unique class of NAD+-dependent deacetylases that regulate diverse biological functions such as aging, metabolism, and stress resistance. Recently, it has been shown that sirtuins may have ... [more ▼]

Sirtuins are a unique class of NAD+-dependent deacetylases that regulate diverse biological functions such as aging, metabolism, and stress resistance. Recently, it has been shown that sirtuins may have anti-inflammatory activities by inhibiting proinflammatory transcription factors such as NF-κB. In contrast, we report in this study that pharmacological inhibition of sirtuins dampens adaptive Th2 responses and subsequent allergic inflammation by interfering with lung dendritic cell (DC) function in a mouse model of airway allergy. Using genetic engineering, we demonstrate that sirtuin 1 represses the activity of the nuclear receptor peroxisome proliferator-activated receptor-γ in DCs, thereby favoring their maturation toward a pro-Th2 phenotype. This study reveals a previously unappreciated function of sirtuin 1 in the regulation of DC function and Th2 responses, thus shedding new light on our current knowledge on the regulation of inflammatory processes by sirtuins. [less ▲]

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See detailEffects of formoterol and ipratropium bromide on repeated cadmium inhalation -induced pulmonary inflammation and emphysema in rats
Zhang, Whenhui; Fievez, Laurence ULg; Zhang, F. et al

in European Journal of Pharmacology (2010), 25(647), 178-187

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See detailSirtuin inhibition modulates endotoxin-induced lung inflammation
Fernandez, C. A.; Fievez, Laurence ULg; Bureau, Fabrice ULg et al

in Shortbook: Annual Congress of the European Respiratory Society (ERS) (2010)

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See detailEffects of ipratropium bromide on repeated cadmium inhalation-induced lune inflammation and airspace enlargement in rats
Zhang, W. H.; Fievez, Laurence ULg; Cheu, Esteban ULg et al

in Fundamental & Clinical Pharmacology (2010), 10

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

in European Journal of Pharmacology (2010), 628(1-3), 171-178

In this study, the anti-inflammatory properties of formoterol and ipratropium bromide, alone or in combination, were investigated in a rat model of acute pulmonary inflammation induced by cadmium ... [more ▼]

In this study, the anti-inflammatory properties of formoterol and ipratropium bromide, alone or in combination, were investigated in a rat model of acute pulmonary inflammation induced by cadmium inhalation. Airway resistance and inflammatory responses, including matrix metalloproteinease-2 (MMP-2) and matrix metalloproteinease-9 (MMP-9) activities, were evaluated. Compared to values obtained in rats exposed to cadmium, pretreatment by bronchodilators administered alone significantly prevented the cadmium-induced increase of airway resistance. Formoterol elicited a significant decrease in total cell number, neutrophil and macrophage counts in bronchoalveolar lavage fluid, whereas ipratropium bromide reduced neutrophil numbers. The two compounds administered alone significantly attenuated the lung lesions associated with parenchyma inflammatory cell influx and congestion observed in the cadmium group. The increased MMP-9 activity was significantly attenuated. Although only formoterol induced a decrease protein concentration in bronchoalveolar lavage fluid, both compounds inhibited the pulmonary edema by reducing wet-to-dry weight ratio which returned to values similar to those recorded in the sham group. All the effects of formoterol on the cadmium-induced inflammatory responses were reversed by propranolol. Similar anti-inflammatory effects were obtained in rats pretreated with ilomastat which showed a significant reduction on inflammatory cell infiltration and MMP-9 activity in bronchoalveolar lavage fluid. Neither synergistic nor additive effects were obtained when the two bronchodilators were administered in combination. In conclusion, formoterol and ipratropium bromide partially protect the lungs against the inflammation by reducing neutrophilic infiltration. This protective effect is associated with reduced MMP-9 activity known to play an important pro-inflammatory role in acute inflammatory process. [less ▲]

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See detailCytokine expression by Aspergillus fumigatus stimulated peripheral blood mononuclear cells from dogs with sino-nasal aspergillosis.
Vanherberghen, Morgane ULg; Bureau, Fabrice ULg; Peters, I. R. et al

in Proceedings of the 20th Annual Congress of the ECVIM-CA (2010)

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See detailEssential role of sirtuins in the pathogenesis of allergic airway inflammation
Legutko, Agnieszka ULg; Marichal, Thomas ULg; Fievez, Laurence ULg et al

in Short book of the Annual Congress of the European Respiratory Society (ERS), Vienne (2009)

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See detailLocal administration of nicotinamide enhances neutrophil apoptosis and decreases mice endotoxin-induced airway inflammation
Fernandes, C. A.; Fievez, Laurence ULg; Ucakar, B. et al

in Société Belge de Sciences Pharmaceutiques (2009)

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See detailEffects of betamethasone on inflammation and emphysema induced by cadmium nebulisation in rats
Fievez, Laurence ULg; Kirschvink, N.; Zhang, Wenhui H. et al

in European Journal of Pharmacology (2009), 606(1-3), 210-214

Cadmium (Cd) induces centrilobular emphysema and is suspected to contribute to tobacco related lung diseases as chronic obstructive pulmonary disease (COPD). This study aimed to check whether the ... [more ▼]

Cadmium (Cd) induces centrilobular emphysema and is suspected to contribute to tobacco related lung diseases as chronic obstructive pulmonary disease (COPD). This study aimed to check whether the inflammatory process observed in rats exposed to nebulised Cd is resistant to betamethasone as observed in COPD and to determine the influence of this drug on airspace enlargement together with the MMP-2-9/TIMP-1-2 imbalance. Our results showed that betamethasone induced emphysema by itself in healthy rats. Moreover, pre-treatment of rats with betamethasone could only partially modulate the increase in bronchoalveolar lavage fluid cell counts and the absence of preventive effect of this compound against emphysema development is associated with its inability to rebalance the MMP-2-9/TIMP-1-2 ratio. [less ▲]

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See detailCharacterization of pentraxin 3 in the horse and its expression in airways.
Ramery, Eve ULg; Fievez, Laurence ULg; Fraipont, Audrey ULg et al

in Veterinary Research (2009), 41(2), 18

The long pentraxin 3 (PTX3) plays an important role in host defence and its over-expression may contribute to airway injury. The aim of the present study was therefore to characterize in more detail PTX3 ... [more ▼]

The long pentraxin 3 (PTX3) plays an important role in host defence and its over-expression may contribute to airway injury. The aim of the present study was therefore to characterize in more detail PTX3 and its expression in the horses airway. Six healthy horses and six horses affected by recurrent airway obstruction (R.A.O.) were submitted to a dusty environment challenge. PTX3 DNA and cDNA were cloned and sequenced. PTX3 expression was evaluated by RT-qPCR, western blotting and immuno-histochemistry in bronchoalveolar lavage fluid (BALF) cells, BALF supernatant and bronchial epithelial cells. An alternative splicing of the second exon of PTX3 occurred, resulting in two forms of the protein: spliced (32 kDa) and full length (42 kDa). PTX3 was detected in BALF macrophages, neutrophils and bronchial epithelial cells. It was over-expressed in the BALF supernatant from R.A.O.-affected horses in crisis. However, dust was unable to induce PTX3 in BALF cells ex vivo, indicating that dust is an indirect inducer of PTX3. Dust exposure in-vivo induced PTX3 in BALF macrophages but there was no significant difference between healthy and R.A.O.-affected horses. Conversely, PTX3 was over-expressed in the bronchial epithelial cells from R.A.O-affected horses in crisis. These data indicate a differential regulatory mechanism in inflammatory and bronchial epithelial cells and offer therapeutically interesting perspectives. [less ▲]

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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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