References of "Horion, Julie"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailDNA methylation and cancer diagnosis: new methods and applications.
Dehan, Pierre ULg; Kustermans, Gaëlle ULg; Guénin, Samuel ULg et al

in Expert Review of Molecular Diagnostics (2009), 9(7), 651-7

Methylation of cytosines in cytosine-guanine (CpG) dinucleotides is one of the most important epigenetic alterations in animals. The presence of methylcytosine in the promoter of specific genes has ... [more ▼]

Methylation of cytosines in cytosine-guanine (CpG) dinucleotides is one of the most important epigenetic alterations in animals. The presence of methylcytosine in the promoter of specific genes has profound consequences on local chromatin structure and on the regulation of gene expression. Changes in DNA methylation play a central role in carcinogenesis. Hypermethylation and consecutive transcriptional silencing of tumor-suppressor genes has been documented in numerous cancers. The identification of target genes silenced by this modification has a great impact on diagnosis, classification, definition of risk groups and prognosis of cancer patients. Here we outline genome-wide techniques aiming at the identification of relevant methylated promoters. Methods and applications allowing clinicians to monitor the methylation of target genes will be also reviewed. [less ▲]

Detailed reference viewed: 77 (17 ULg)
Full Text
Peer Reviewed
See detailActin cytoskeleton differentially modulates NF-κB-mediated IL-8 expression in myelomonocytic cells
Kustermans, Gaëlle ULg; El Mjiyad, Nadia ULg; Horion, Julie ULg et al

in Biochemical Pharmacology (2008), 76(10)

Many physiopathological events such as phagocytosis, pathogen invasion, cellular adhesion and chemotaxis governed by actin-based cytoskeleton are often accompanied by nuclear factor kB (NF-kB) activation ... [more ▼]

Many physiopathological events such as phagocytosis, pathogen invasion, cellular adhesion and chemotaxis governed by actin-based cytoskeleton are often accompanied by nuclear factor kB (NF-kB) activation and expression of pro-inflammatory genes. In the present study, we demonstrated that reorganization of actin cytoskeleton induced by Cytochalasin D (CytD), an actin-polymerization inhibitor, enhanced il-8 gene expression induced by TNFa and LPS in HL-60 monocyte-like cells. Both transcriptional and post-transcriptional mechanisms were involved. CytD potentiated NF-kB-mediated transcription induced by both TNFa and LPS but via different mechanisms. In the case of LPS, the perturbation of actin dynamics increased the TLR4 levels at the cell membrane and consequently enhanced the IKK complex activation and NF-kB nuclear translocation. However, the canonical pathway involving the IKK complex and leading to the NF-kB translocation into the nucleus was not affected by actin remodelling in the case of TNFa. Interestingly, actin disruption primed p65 phosphorylation induced by TNFa and LPS, on Ser276 and Ser536, respectively, which suggested actin cytoskeleton could also modulate p65 transactivating activity. [less ▲]

Detailed reference viewed: 77 (23 ULg)
Full Text
Peer Reviewed
See detailHistone deacetylase inhibitor trichostatin A sustains sodium pervanadate-induced NF-kappa B activation by delaying IkappaBalpha mRNA resynthesis : comparison with tumor necrosis factor alpha
Horion, Julie ULg; Gloire, Geoffrey ULg; El Mjiyad, Nadia et al

in Journal of Biological Chemistry (2007), 282(21), 15383

NF-kappaB is a crucial transcription factor tightly regulated by protein interactions and post-translational modifications, like phosphorylation and acetylation. A previous study has shown that ... [more ▼]

NF-kappaB is a crucial transcription factor tightly regulated by protein interactions and post-translational modifications, like phosphorylation and acetylation. A previous study has shown that trichostatin A (TSA), a histone deacetylase inhibitor, potentiates tumor necrosis factor (TNF) alpha-elicited NF-kappaB activation and delays IkappaBalpha cytoplasmic reappearance. Here, we demonstrated that TSA also prolongs NF-kappaB activation when induced by the insulino-mimetic pervanadate (PV), a tyrosine phosphatase inhibitor that initiates an atypical NF-kappaB signaling. This extension is similarly correlated with delayed IkappaBalpha cytoplasmic reappearance. However, whereas TSA causes a prolonged IKK activity when addedtoTNFalpha, it does notwhenaddedtoPV.Instead, quantitative reverse transcriptase-PCR revealed a decrease of ikappabalphamRNAlevel after TSA addition to PV stimulation. This synthesis deficit of the inhibitor could explain the sustained NF-kappaB residence in the nucleus. In vivo analysis by chromatin immunoprecipitation assays uncovered that, forPVinduction but not forTNFalpha, the presence of TSA provokes several impairments on the ikappabalphapromoter: (i) diminution of RNA Pol II recruitment; (ii) reduced acetylation and phosphorylation of histone H3-Lys14 and -Ser10, respectively; (iii) decreased presence of phosphorylated p65-Ser536; and (iv) reduction of IKKalphabinding. The recruitment of these proteins on the icam-1 promoter, another NF-kappaB-regulated gene, is not equally affected, suggesting a promoter specificity of PV with TSA stimulation. Taken together, these data suggest that TSA acts differently depending on the NF-kappaB pathway and the targeted promoter in question. This indicates that one overall histone deacetylase role is to inhibit NF-kappaB activation by molecular mechanisms specific of the stimulus and the promoter. [less ▲]

Detailed reference viewed: 29 (8 ULg)
Full Text
Peer Reviewed
See detailVaricella-zoster virus modulates NF-kappaB recruitment on selected cellular promoters.
El Mjiyad, Nadia ULg; Bontems, Sébastien ULg; Gloire, Geoffrey ULg et al

in Journal of Virology (2007), 81(23), 13092-104

Intercellular adhesion molecule 1 (ICAM-1) expression is down-regulated in the center of cutaneous varicella lesions despite the expression of proinflammatory cytokines such as gamma interferon and tumor ... [more ▼]

Intercellular adhesion molecule 1 (ICAM-1) expression is down-regulated in the center of cutaneous varicella lesions despite the expression of proinflammatory cytokines such as gamma interferon and tumor necrosis factor alpha (TNF-alpha). To study the molecular basis of this down-regulation, the ICAM-1 induction of TNF-alpha was analyzed in varicella-zoster virus (VZV)-infected melanoma cells (MeWo), leading to the following observations: (i) VZV inhibits the stimulation of icam-1 mRNA synthesis; (ii) despite VZV-induced nuclear translocation of p65, p52, and c-Rel, p50 does not translocate in response to TNF-alpha; (iii) the nuclear p65 present in VZV-infected cells is no longer associated with p50 and is unable to bind the proximal NF-kappaB site of the icam-1 promoter, despite an increased acetylation and accessibility of the promoter in response to TNF-alpha; and (iv) VZV induces the nuclear accumulation of the NF-kappaB inhibitor p100. VZV also inhibits icam-1 stimulation of TNF-alpha by strongly reducing NF-kappaB nuclear translocation in MRC5 fibroblasts. Taken together, these data show that VZV interferes with several aspects of the immune response by inhibiting NF-kappaB binding and the expression of target genes. Targeting NF-kappaB activation, which plays a central role in innate and adaptive immune responses, leads to obvious advantages for the virus, particularly in melanocytes, which are a site of viral replication in the skin. [less ▲]

Detailed reference viewed: 91 (18 ULg)
Full Text
Peer Reviewed
See detailWithaferin a strongly elicits IkappaB kinase beta hyperphosphorylation concomitant with potent inhibition of its kinase activity
Kaileh, Mary; Vanden Berghe, Wim; Heyerick, Arne et al

in Journal of Biological Chemistry (2007), 282(7), 4253

The transcription factor NFkappaB plays a critical role in normal and pathophysiological immune responses. Therefore, NFkappaB and the signaling pathways that regulate its activation have become a major ... [more ▼]

The transcription factor NFkappaB plays a critical role in normal and pathophysiological immune responses. Therefore, NFkappaB and the signaling pathways that regulate its activation have become a major focus of drug development programs. Withania somnifera (WS) is a medicinal plant that is widely used in Palestine for the treatment of various inflammatory disorders. In this study we show that the leave extract of WS, as well as its major constituent withaferin A (WA), potently inhibits NFkappaB activation by preventing the tumor necrosis factor-induced activation of IkappaB kinase beta via a thioalkylation-sensitive redox mechanism, whereas other WS-derived steroidal lactones, such as withanolide A and 12-deoxywithastramonolide, are far less effective. To our knowledge, this is the first communication of IkappaB kinase beta inhibition by a plant-derived inhibitor, coinciding with MEK1/ERK-dependent Ser-181 hyperphosphorylation. This prevents IkappaB phosphorylation and degradation, which subsequently blocks NFkappaB translocation, NFkappaB/DNA binding, and gene transcription. Taken together, our results indicate that pure WA or WA-enriched WS extracts can be considered as a novel class of NFkappaB inhibitors, which hold promise as novel anti-inflammatory agents for treatment of various inflammatory disorders and/or cancer. [less ▲]

Detailed reference viewed: 28 (4 ULg)