References of "Legrand, Sylvie"
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See detailInflammation as a link between obesity, metabolic syndrome and type 2 diabetes
ESSER, Nathalie ULg; Legrand, Sylvie ULg; Piette, Jacques ULg et al

in Diabetes Research & Clinical Practice (2014)

It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic ... [more ▼]

It is recognized that a chronic low-grade inflammation and an activation of the immune system are involved in the pathogenesis of obesity-related insulin resistance and type 2 diabetes. Systemic inflammatory markers are risk factors for the development of type 2 diabetes and its macrovascular complications. Adipose tissue, liver, muscle and pancreas are themselves sites of inflammation in presence of obesity. An infiltration of macrophages and other immune cells is observed in these tissues associated with a cell population shift from an anti-inflammatory to a pro-inflammatory profile. These cells are crucial for the production of pro-inflammatory cytokines, which act in an autocrine and paracrine manner to interfere with insulin signaling in peripheral tissues or induce β-cell dysfunction and subsequent insulin deficiency. Particularly, the pro-inflammatory interleukin-1β is implicated in the pathogenesis of type 2 diabetes through the activation of the NLRP3 inflammasome. The objectives of this review are to expose recent data supporting the role of the immune system in the pathogenesis of insulin resistance and type 2 diabetes and to examine various mechanisms underlying this relationship. If type 2 diabetes is an inflammatory disease, anti-inflammarory therapies could have a place in prevention and treatment of type 2 diabetes. [less ▲]

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See detailUnsaturated fatty acids prevent activation of NLRP3 inflammasome in human monocytes/macrophages
L'Homme, Laurent ULg; Esser, Nathalie ULg; Riva, Laura ULg et al

in Journal of Lipid Research (2013), 54

The NLRP3 inflammasome is involved in many obesity-associated diseases such as type 2 diabetes, atherosclerosis and gouty arthritis through its ability to induce IL-1β release. The molecular link between ... [more ▼]

The NLRP3 inflammasome is involved in many obesity-associated diseases such as type 2 diabetes, atherosclerosis and gouty arthritis through its ability to induce IL-1β release. The molecular link between obesity and inflammasome activation is still unclear but free fatty acids have been proposed as one triggering event. Here we reported opposite effects of saturated fatty acids (SFAs) compared to unsaturated fatty acids (UFAs) on NLRP3 inflammasome in human monocytes/macrophages. Palmitate and stearate, both SFAs, triggered IL-1β secretion in a caspase-1/ASC/NLRP3-dependent pathway. Unlike SFAs, the UFAs oleate and linoleate did not lead to IL-1β secretion. In addition, they totally prevented the IL-1β release induced by SFAs and, with less efficiency, by a broad range of NLRP3 inducers including nigericin, alum and MSU. UFAs did not affect the transcriptional effect of SFAs suggesting a specific effect on the NLRP3 activation. These results provide a new antiinflammatory mechanism of UFAs by preventing the activation of the NLRP3 inflammasome and therefore the IL-1β processing. By this way, UFAs might play a protective role in NLRP3-associated diseases. [less ▲]

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See detailThe inositol phosphatase SHIP-1 inhibits NOD2-induced NF-κB activation by disturbing the interaction of XIAP with RIP2
Condé, Claude ULg; Rambout, Xavier ULg; Lebrun, Marielle ULg et al

in PLoS ONE (2012)

SHIP-1 is an inositol phosphatase predominantly expressed in hematopoietic cells. Over the ten past years, SHIP-1 has been described as an important regulator of immune functions. Here, we characterize a ... [more ▼]

SHIP-1 is an inositol phosphatase predominantly expressed in hematopoietic cells. Over the ten past years, SHIP-1 has been described as an important regulator of immune functions. Here, we characterize a new inhibitory function for SHIP-1 in NOD2 signaling. NOD2 is a crucial cytoplasmic bacterial sensor that activates proinflammatory and antimicrobial responses upon bacterial invasion. We observed that SHIP-1 decreases NOD2-induced NF-κB activation in macrophages. This negative regulation relies on its interaction with XIAP. Indeed, we observed that XIAP is an essential mediator of the NOD2 signaling pathway that enables proper NF-κB activation in macrophages. Upon NOD2 activation, SHIP-1 C-terminal proline rich domain (PRD) interacts with XIAP, thereby disturbing the interaction between XIAP and RIP2 in order to decrease NF-κB signaling. [less ▲]

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See detailActin-targeting natural compounds as tools to study the role of actin cytoskeleton in signal transduction.
Kustermans, Gaëlle ULg; Piette, Jacques ULg; Legrand, Sylvie ULg

in Biochemical Pharmacology (2008), 76(11)

Actin cytoskeleton controls a vast range of cellular processes such as motility, cytokinesis, differentiation, vesicle transport, phagocytosis, muscle contraction. A growing literature clearly ... [more ▼]

Actin cytoskeleton controls a vast range of cellular processes such as motility, cytokinesis, differentiation, vesicle transport, phagocytosis, muscle contraction. A growing literature clearly demonstrated that actin cytoskeleton can play a regulating role in several signalling pathways. Cells tightly regulate actin dynamics through numerous specific proteins in order to rapidly and locally respond to various stimuli. An obvious approach to determine the involvement of actin cytoskeleton in signalling pathways is the use of actin-targeting natural compounds. These drugs modulate actin dynamics, accelerating either polymerization or depolymerization, through various mechanisms. This review focus on the use of these actin-targeting drugs as tools to demonstrate the role of actin cytoskeleton in several signal transduction pathways such as those initiated from antigen receptor in T and B cells or those involving mitogen-activated protein kinases (MAPKs) or transcription factors NF-kB and SRF (serum response factor). In this last case (SRF), the use of various actin-targeting drugs participated in the elucidation of the molecular mechanism by which actin regulates SRF-mediated transcription. [less ▲]

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See detailModulation of Nod2-dependent NF-kappa B signaling by the actin cytoskeleton
Legrand, Sylvie ULg; Kustermans, Gaëlle ULg; Bex, Françoise et al

in Journal of Cell Science (2007), 120(7), 1299-1310

Actin disruption by CytochalasinD (CytD) and LatrunculinB (LatB) induced NF-kappa B activation in myelomonocytic and intestinal epithelial cells. In an attempt to elucidate the mechanism by which actin ... [more ▼]

Actin disruption by CytochalasinD (CytD) and LatrunculinB (LatB) induced NF-kappa B activation in myelomonocytic and intestinal epithelial cells. In an attempt to elucidate the mechanism by which actin disruption induced IKK activation, we studied the human Nod2 protein, which was able to induce NF-kappa B activation and whose expression was restricted to myelomonocytic and intestinal epithelial cells. Nod2 is thought to play key roles in pathogen defence through sensing bacteria and generating an inflammatory immune response. We showed that actin disruption by CytD significantly and specifically increased Nod2-mediated NF-kappa B signaling. Nod2 was fully partitioned in the Triton-X-100-insoluble fraction but translocated into the soluble fraction after CytD treatment, demonstrating that the presence of Nod2 in the detergent-insoluble pellet was specific to actin cytoskeleton. Confocal analysis also revealed a Nod2 colocalization with membrane-associated F-actin. Colocalization and co-immunoprecipitation assays with endogenous Rac1 have shown that Nod2 associated with activated Rac1 in membrane ruffles through both its N-terminal caspase recruitment domains (CARD) and C-terminal leucine-rich repeats (LRRs). Membrane ruffle disruption by a Rac1 dominant negative form primed Nod2-dependent NF-kappa B signaling. The recruitment of Nod2 in Rac-induced dynamic cytoskeletal structures could be a strategy to both repress the Nod2-dependent NF-kappa B signaling in unstimulated cells and rapidly mobilize Nod2 during bacterial infection. [less ▲]

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See detailPerturbation of actin dynamics induces NF-kappa B activation in myelomonocytic cells through an NADPH oxidase-dependent pathway
Kustermans, Gaëlle ULg; El Benna, Jamel; Piette, Jacques ULg et al

in Biochemical Journal (2005), 387(Pt 2), 531-540

Although several reports showed the effect of compounds disrupting microtubules on NF-kappa B (nuclear factor kappa B) activation, nothing is known about agents perturbing actin dynamics. In the present ... [more ▼]

Although several reports showed the effect of compounds disrupting microtubules on NF-kappa B (nuclear factor kappa B) activation, nothing is known about agents perturbing actin dynamics. In the present study, we have shown that actin cytoskeleton disruption induced by actin-depolymerizing agents such as cytochalasin D and latrunculin B and actin-polymerizing compounds such as jasplakinolide induced NF-kappa B activation in myelomonocytic cells. The transduction pathway involved the I kappa B (inhibitory kappa B) kinase complex and a degradation of I kappa B alpha. We have shown that NF-kappa B activation in response to the perturbation of actin dynamics required reactive oxygen species. as demonstrated by the effect of antioxidants. Actin cytoskeleton disruption by cytochalasin D induced O-2(-) release from human monocytes, through the activation of the NADPH oxidase, as confirmed by the phosphorylation and by the membrane translocation of p47(phox). NF-kappa B activation after actin cytoskeleton disruption could be physiologically relevant during monocyte activation and/or recruitment into injured tissues, where cellular attachment, migration and phagocytosis result in cyclic shifts in cytoskeletal organization and disorganization. [less ▲]

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See detailStimulation of glutatione-peroxidase activity decreases HIV type-1 activation after oxidative stress
Sappey, C.; Legrand, Sylvie ULg; Best-Belopmme, M. et al

in AIDS Research and Human Retroviruses (1994), 10(11), 1451-1461

Am important aspect of human immunodeficiency virus (HIV-1) infection is the regulation of its expression by nuclear factor kappa B (NF-kappa B) by redox-controlled signal transduction pathways. In this ... [more ▼]

Am important aspect of human immunodeficiency virus (HIV-1) infection is the regulation of its expression by nuclear factor kappa B (NF-kappa B) by redox-controlled signal transduction pathways. In this study, we demonstrate that selenium supplementation can effectively increase glutathione peroxidase (GPx) activity in latently infected T lymphocytes. The Se-supplemented cells exhibited an important protection against the cytotoxic and reactivating effects of hydrogen peroxide (H2O2). Concomitantly, NF-kappa B activation by H2O2 was also decreased in Se-supplemented cells. Selenium stimulation of GPx activity also induces a protective effect against cell activation by tumor necrosis factor alpha (TNF-alpha) but less significantly by phorbol esters such as PMA. These Se-mediated effects were specific because they were not found when AP-1 DNA-binding activity was studied after H2O2-induced stress. Hyperthermia was also studied because it could promote intracellular electron leakage in electron transport chains. Elevating the temperature to 42 degrees C did not induce NF-kappa B directly. Rather, it sensitized infected cells to subsequent oxidative stress by H2O2, demonstrating the importance of hyperthermia, often associated with opportunistic infections in the development of immunodeficiency. In this case, Se induced partial protection against the sensitizing effect of hyperthermia. [less ▲]

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See detailHIV-1 promoter activation following an oxidative stress mediated by singlet oxygen
Legrand, Sylvie ULg; Hoebeke, Maryse ULg; Vaira, Dolorès ULg et al

in Journal of Photochemistry and Photobiology B : Biology (1993), 17(3), 229-237

Various biological processes, such as photosensitization or inflammatory reactions, can generate singlet oxygen (O-1(2)) as one of the major oxidative species. Because this oxidant can be generated either ... [more ▼]

Various biological processes, such as photosensitization or inflammatory reactions, can generate singlet oxygen (O-1(2)) as one of the major oxidative species. Because this oxidant can be generated either extracellularly or intracellularly, it can cause severe damage to various biological macromolecules, even to those deeply embedded inside the cells such as DNA. Sublethal biological modifications induced by different DNA-damaging agents can promote various cellular responses initiated by the activation of various cellular genes and certain heterologous viruses. Since O-1(2) fulfils essential prerequisites for a genotoxic substance, we have examined the effects of an oxidative stress, mediated by this species, on cells harbouring a heterologous promoter-leader sequence derived from the human immunodeficiency virus type 1 (HIV-1). Our results demonstrate that HIV-1 long terminal repeat (LTR), integrated into the cellular I)NA of epithelial cells, can be transactivated following an oxidative stress mediated by O-1(2). In addition, using HIV-1 latently infected promonocytes or lymphocytes, it can be shown that virus reactivation can be induced through a sublethal dose of O-1(2) generated intracellularly. An extracellular generation of O-1(2) can promote a substantial lethal effect without HIV-1 reactivation. These data may be relevant to the understanding of the events converting a latent infection into a productive one and to the appearance of the acquired immune deficiency syndrome. [less ▲]

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See detailHIV-1 reactivation after an oxidative stress
Legrand, Sylvie ULg; Vaira, Dolorès ULg; Rentier, Bernard ULg et al

in LinkVIII International Conference on AIDS/III STD World Congress, Amsterdam, the Netherlands 19-24 July 1992 (1992)

OBJECTIVES: A common denominator shared by several HIV-1 reactivation agents such as certain cytokines, UV irradiation and heat shock is their ability to cause stress response. Consequently, we have ... [more ▼]

OBJECTIVES: A common denominator shared by several HIV-1 reactivation agents such as certain cytokines, UV irradiation and heat shock is their ability to cause stress response. Consequently, we have investigated the effects of oxidative stress on HIV-1 reactivation, knowing that HIV-1 latently infected T cells can be exposed in vivo to such a stress when blood phagocytes are stimulated during inflammatory reactions. METHODS: The promonocytic (U1) and lymphocytic (ACH-2) cell lines, both HIV-1 chronically infected, were used to study the reactivation phenomenon. To test wether HIV-1 reactivation is mediated by LTR transactivation, the HeLa HIV-1 CAT cell line, which carries an integrated DNA cartridge containing CAT gene under control of HIV-1 LTR, was also exposed to an oxidative stress. RESULTS: Hydrogen peroxide exposure of U1 cells leads to an increased reverse transcriptase (RT) activity in supernatant fluid. Over the optimal concentrations range (0.5 to 1 mM), a four to fivefold stimulation level is reached. Below these concentrations, stress conditions are not sufficient and above, they induce a too important lethal effect. Immunofluorescence carried out on stressed U1 cells shows that H2O2 leads to HIV-1 gene expression activation and not to a release of viral particles from damaged cells. H2O2 also induces a stimulation of CAT activity in HeLa HIV-1 CAT cells. Intracellular singulet oxygen (1O2) is also able to induce an increase of RT activity in supernatant fluid of U1 and ACH-2 cells and a stimulation of CAT activity in HeLa HIV-1 CAT cells. A dose-response curve can also be demonstrated. In order to transpose these in vitro experiments to situations encountered in vivo, activated phagocytes were cocultivated with HeLa HIV-1 CAT cells. A weak stimulation of CAT activity was detected. CONCLUSIONS: Cellular oxidative damages induce HIV-1 LTR transactivation leading to viral gene expression and consequently to a burst of virus production. DNA damages induced by oxidative stress could be at the onset of HIV-1 reactivation. Experiments are now in progress to elucidate the mechanisms leading to HIV-1 reactivation after an oxidative stress. [less ▲]

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See detailHIV-1 reactivation after an oxidative stress
Legrand, Sylvie ULg; Hoebeke, Maryse ULg; Vaira, Dolorès ULg et al

in Archives Internationales de Physiologie, de Biochimie et de Biophysique (1992), 100

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