References of "Ehx, Grégory"
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See detailLiver proteomic response to hypertriglyceridemia in human-apolipoprotein C-III transgenic mice at cellular and mitochondrial compartment levels
Ehx, Grégory ULg; Gerin, Stéphanie ULg; Mathy, Grégory et al

in Lipids in Health and Disease (2014), 13

Background: Hypertriglyceridemia (HTG) is defined as a triglyceride (TG) plasma level exceeding 150 mg/dl and is tightly associated with atherosclerosis, metabolic syndrome, obesity, diabetes and acute ... [more ▼]

Background: Hypertriglyceridemia (HTG) is defined as a triglyceride (TG) plasma level exceeding 150 mg/dl and is tightly associated with atherosclerosis, metabolic syndrome, obesity, diabetes and acute pancreatitis. The present study was undertaken to investigate the impact of hypertriglyceridemia on the mitochondrial, sub-mitochondrial and cellular proteomes in the hepatocytes of a hypertriglyceridemic transgenic mouse model overexpressing the human apolipoproteinC-III. Methods: Quantitative comparative proteomics (2D-DIGE) was carried out in both “low-expressor” (LE) and “high-expressor” (HE) mice, respectively exhibiting moderate and severe HTG, to characterize the effect of the TG plasma level on the proteomic response. Results: The mitoproteome analysis revealed the occurrence of a large-scale adaptation in transgenic mice consisting of a general down-regulation of matricial proteins and up-regulation of inner membrane proteins. Remarkably, the magnitude of these proteomic changes appears to strongly depend on the TG plasma level. Altogether, our different analyses indicate that, in HE mice, the capacity of several metabolic pathways is altered to promote the availability of acetyl-CoA, glycerol-3-phosphate, ATP and NADPH for de novo TG biosynthesis. The up-regulation of several cytosolic ROS detoxifying enzymes also tend to confirm that the cytoplasm of HTG mice is subjected to oxidative stress as previously stated. The up-regulation of cytosolic ferritin indicates that iron over-accumulation could take place in the cytosol of HE mice hepatocytes and contribute to (i) enhance oxidative stress and (ii) promote cellular proliferation. Conclusions: The present analyses demonstrate that important TG dose-responsive metabolic adaptations are set up in human apolipoproteinC-III-overexpressing mice. Our results indicate that these adaptations could support the higher TG production rates which have been previously reported in this HTG model, and also suggest that cytosolic oxidative stress may result from FFA over-accumulation, iron overload and enhanced activity of some ROS-producing catabolic enzymes. [less ▲]

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See detailXenogeneic GVHD in NSG mice: focus on rapamycin
Ehx, Grégory ULg

Conference (2014, April 11)

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See detailImmunomodulatory effects of Rapamycin in xenogeneic GVHD
Ehx, Grégory ULg

Poster (2014, January 31)

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Several studies have shown that rapamycin (RAPA), an mTOR ... [more ▼]

Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Several studies have shown that rapamycin (RAPA), an mTOR inhibitor with immunosuppressive properties, may reduce GVHD severity and mortality, notably by favoring regulatory T cells (Tregs) proliferation in vivo and in vitro. However, very few data have been reported about the global impact of this drug on the immune system in the context of GVHD. The present work investigates the cellular mechanisms by which RAPA delays death from xenogeneic GVHD induced by peripheral blood mononuclear cells infusion in NSG mice. Our results show that RAPA injections significantly delay death from xenogeneic GVHD and reduce disease severity. Flow cytometric analyses highlighted a strong reduction of human cells chimerism in mice together with higher CD4+/CD8+ T cells balance due to a lower proliferation of CD8+ T cells. In addition, the frequencies of naive CD4+ and CD8+ T cells were higher and the CD4+ T cells showed a reduced effector phenotype (CD45RO+CD27-). Tregs were positively affected as RAPA up-regulated their expression of Bcl-2 and Ki67 as well as their STAT5 phosphorylation level, leading to higher Treg frequency in treated mice. Altogether these data demonstrate that RAPA delays xenogeneic GVHD by lowering human chimerism and effector CD4+ frequency as well as promoting Tregs. [less ▲]

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See detailImmunomodulatory effects of Rapamycin in xenogeneic GVHD
Ehx, Grégory ULg; HANNON, Muriel ULg; DUBOIS, Sophie ULg et al

Poster (2014, January 27)

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See detailThinking out of the box - New approaches to controlling GVHD
Baron, Frédéric ULg; Humblet-Baron, Stéphanie; Ehx, Grégory ULg et al

in Current Hematologic Malignancy Reports (2014), 9

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Despite major advances in the understanding of GVHD pathogenesis, standard GVHD ... [more ▼]

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Despite major advances in the understanding of GVHD pathogenesis, standard GVHD prophylaxis regimens continue to bebased on the combination of a calcineurin inhibitor with an antimetabolite, while first line treatmentsstill relies on high-dose corticosteroids. Further, no second line treatment has emerged thus far in acute or chronic GVHD patients who failed on corticosteroids. After briefly reviewing current standards of GVHD prevention and treatment, this article will discuss recent approaches that might change GVHD prophylaxis / treatment in the next decades, with a special focus on recently developed immunoregulatory strategies based on infusion of mesenchymal stromal or regulatory T-cells, or on injection of lowdose interleukin-2. [less ▲]

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See detailEtude protéomique de l'incidence d'une hypertriglycéridémie sur le métabolisme hépatique de la souris
Ehx, Grégory ULg

Master's dissertation (2011)

L’hypertriglycéridémie est une pathologie largement répandue chez l’homme sédentarisé. Elle se définit comme un taux plasmatique de triglycérides (TAG) anormalement élevé (supérieur à 200 mg/dl). La ... [more ▼]

L’hypertriglycéridémie est une pathologie largement répandue chez l’homme sédentarisé. Elle se définit comme un taux plasmatique de triglycérides (TAG) anormalement élevé (supérieur à 200 mg/dl). La souris transgénique HuApoC-III est un animal modèle idéal pour l’étude de l’hypertriglycéridémie indépendamment des effets confondants qui y sont généralement associés (en particulier l’obésité et la résistance à l’insuline). En effet, elles sont hypertriglycéridémiques mais ne sont ni obèses ni résistantes à l’insuline. Dans la continuité d’une étude des adaptations mitoprotéomiques hépatique à une hypertriglycéridémie sévère (taux de TAG supérieur à 500 mg/dl) récemment menée par notre laboratoire, nous avons caractérisé par une technique de protéomique comparative, le 2DDIGE, les adaptations protéomiques de la membrane interne mitochondriale et du protéome cellulaire à ce même type d’hypertriglycéridémie, chez la souris HuApoC-III. Comme prédit lors de notre étude antérieure, le protéome de la membrane interne s’est avéré ne présenter aucune modification de sa composition entre les souris HuApoC-III et sauvages. Comme il a été rapporté que les souris HuApoC-III présentent une vitesse de respiration mitochondriale à l’état III sur succinate similaire à celle des souris sauvages, cette invariance de la composition protéique de la membrane interne pourrait refléter des altérations de sa composition lipidique ou de sa structure. L’analyse du protéome cellulaire total a permis de confirmer l’augmentation de la capacité du catabolisme des acides aminés et de la glycolyse suggérée par nos résultats antérieurs. Cette augmentation, accompagnée de l’augmentation de la capacité de la β- oxydation également décrite antérieurement, permettrait d’augmenter le taux de production d’acétyl-CoA, de glycérol-3-phosphate et d’ATP fin de supporter la production élevée de TAG des hépatocytes des souris HuApoC-III. Cette analyse a par ailleurs révélé que les hépatocytes des souris HuApoC-III présentent un stress oxydatif cytoplasmique, une probable accumulation de fer intracytoplasmique et une prolifération accrue. Ce stress oxydatif pouvant induire des lésions cellulaires et tissulaires ainsi que l’inflammation du foie, nous proposons que les souris HuApoC-III présentent une fibrose hépatique. [less ▲]

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