References of "Piette, Jacques"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailInduction of the Alternative NF-{kappa}B Pathway by Lymphotoxin {alpha}{beta} (LT{alpha}{beta}) Relies on Internalization of LT{beta} Receptor
Ganeff, Corine; Remouchamps, Caroline ULg; Boutaffala, Layla et al

in Molecular & Cellular Biology (2011), 21

Several tumor necrosis factor receptor (TNFR) family members activate both the classical and the alternative NF-κB pathways. However, how a single receptor engages these two distinct pathways is still ... [more ▼]

Several tumor necrosis factor receptor (TNFR) family members activate both the classical and the alternative NF-κB pathways. However, how a single receptor engages these two distinct pathways is still poorly understood. Using lymphotoxin β receptor (LTβR) as a prototype, we showed that activation of the alternative, but not the classical, NF-κB pathway relied on internalization of the receptor. Further molecular analyses revealed a specific cytosolic region of LTβR essential for its internalization, TRAF3 recruitment, and p100 processing. Interestingly, we found that dynamin-dependent, but clathrin-independent, internalization of LTβR appeared to be required for the activation of the alternative, but not the classical, NF-κB pathway. In vivo, ligand-induced internalization of LTβR in mesenteric lymph node stromal cells correlated with induction of alternative NF-κB target genes. Thus, our data shed light on LTβR cellular trafficking as a process required for specific biological functions of NF-κB. [less ▲]

Detailed reference viewed: 66 (15 ULg)
Full Text
Peer Reviewed
See detailImportance of the PIKKs in NF-kappaB activation by genotoxic stress
Sabatel, Hélène ULg; Pirlot, Céline ULg; Piette, Jacques ULg et al

in Biochemical Pharmacology (2011), 82(10), 1371-83

Detailed reference viewed: 29 (7 ULg)
Full Text
Peer Reviewed
See detailRIP3 Expression Induces a Death Profile Change in U2OS Osteosarcoma Cells After 5-ALA-PDT
Coupienne, Isabelle ULg; Fettweis, Grégory ULg; Piette, Jacques ULg

in Lasers in Surgery and Medicine (2011), 43(7), 557564

Background and Objective The receptor-interacting protein 3 (RIP3) has recently been outlined as a key necrosis mediator but is also thought to participate in the regulation of apoptosis. The aim of this ... [more ▼]

Background and Objective The receptor-interacting protein 3 (RIP3) has recently been outlined as a key necrosis mediator but is also thought to participate in the regulation of apoptosis. The aim of this study is to compare the cell death profile induced by 5-aminolevulic acid (5-ALA)-mediated photodynamic therapy (PDT) in the RIP3-deficient cell line U2OS and in U2OS cells in which the expression of RIP3 was restored. Materials and Methods RIP3-expressing U2OS cells (RIP3-U2OS) were obtained after transfection and antibiotic selection. Wild type and RIP3-U2OS cells were treated by 5-ALA-PDT. Overall cell viability was evaluated and different parameters characteristic of apoptosis, autophagy, and necrosis were studied. Results Surprisingly, the survival of RIP3-U2OS cells was higher compared to that of the wild type cells. In addition, RIP3-U2OS cell death was decreased by a zVAD-fmk pre-treatment. A higher cleavage of caspase-3, 7, 8, 9, and PARP was also detected in these cells, pointing out to the activation of caspase-dependent apoptosis. In parallel, a thrust of autophagy was clearly identified in the RIP3-U2OS cells. Conversely, RIP3-U2OS exhibited a lower level of necrosis than the wild types. Interestingly, necrostatin-1 efficiently decreased necrosis level in RIP3-U2OS but not in wild type cells. Conclusion Expression of RIP3 in U2OS cells led to a better survival but also to a death profile change in response to PDT. The apoptotic and autophagic pathways were clearly up-regulated compared to the RIP3-deficient wild type cells. However, induction of necrosis was weaker in the RIP3-U2OS cells. In this context, autophagy is likely to play a protective role against PDT-induced cell death and to allow a better survival of RIP3-U2OS cells. This work also highlights the important role played by RIP3 in the apoptotic pathway, although the modalities are still widely unknown. [less ▲]

Detailed reference viewed: 33 (14 ULg)
Full Text
Peer Reviewed
See detailNF-kappaB inhibition improves the sensitivity of human glioblastoma cells to 5-aminolevulinic acid-based photodynamic therapy.
Coupienne, Isabelle ULg; Bontems, Sébastien ULg; Dewaele, M. et al

in Biochemical Pharmacology (2011)

Glioblastoma constitute the most frequent and deadliest brain tumors of astrocytic origin. They are very resistant to all current therapies and are associated with a huge rate of recurrence. In most cases ... [more ▼]

Glioblastoma constitute the most frequent and deadliest brain tumors of astrocytic origin. They are very resistant to all current therapies and are associated with a huge rate of recurrence. In most cases, this type of tumor is characterized by a constitutive activation of the nuclear factor-kappaB (NF-kappaB). This factor is known to be a key regulator of various physiological processes such as inflammation, immune response, cell growth or apoptosis. In the present study, we explored the role of NF-kappaB activation in the sensitivity of human glioblastoma cells to a treatment by 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT). 5-ALA is a physiological compound widely used in PDT as well as in tumor photodetection (PDD). Our results show that inhibition of NF-kappaB improves glioblastoma cell death in response to 5-ALA-PDT. We then studied the molecular mechanisms underlying the cell death induced by PDT combined or not with NF-kappaB inhibition. We found that apoptosis was induced by PDT but in an incomplete manner and that, unexpectedly, NF-kappaB inhibition reduced its level. Oppositely PDT mainly induces necrosis in glioblastoma cells and NF-kappaB is found to have anti-necrotic functions in this context. The autophagic flux was also enhanced as a result of 5-ALA-PDT and we demonstrate that stimulation of autophagy acts as a pro-survival mechanism confering protection against PDT-mediated necrosis. These data point out that 5-ALA-PDT has an interesting potential as a mean to treat glioblastoma and that inhibition of NF-kappaB renders glioblastoma cells more sensitive to the treatment. [less ▲]

Detailed reference viewed: 30 (5 ULg)
Full Text
Peer Reviewed
See detailThe varicella-zoster virus ORF47 kinase interferes with host innate immune response by inhibiting the activation of IRF3.
Vandevenne, Patricia ULg; Lebrun, Marielle ULg; El Mjiyad, Nadia et al

in PLoS ONE (2011), 9(2),

The innate immune response constitutes the first line of host defence that limits viral spread and plays an important role in the activation of adaptive immune response. Viral components are recognized by ... [more ▼]

The innate immune response constitutes the first line of host defence that limits viral spread and plays an important role in the activation of adaptive immune response. Viral components are recognized by specific host pathogen recognition receptors triggering the activation of IRF3. IRF3, along with NF-kappaB, is a key regulator of IFN-beta expression. Until now, the role of IRF3 in the activation of the innate immune response during Varicella-Zoster Virus (VZV) infection has been poorly studied. In this work, we demonstrated for the first time that VZV rapidly induces an atypical phosphorylation of IRF3 that is inhibitory since it prevents subsequent IRF3 homodimerization and induction of target genes. Using a mutant virus unable to express the viral kinase ORF47p, we demonstrated that (i) IRF3 slower-migrating form disappears; (ii) IRF3 is phosphorylated on serine 396 again and recovers the ability to form homodimers; (iii) amounts of IRF3 target genes such as IFN-beta and ISG15 mRNA are greater than in cells infected with the wild-type virus; and (iv) IRF3 physically interacts with ORF47p. These data led us to hypothesize that the viral kinase ORF47p is involved in the atypical phosphorylation of IRF3 during VZV infection, which prevents its homodimerization and subsequent induction of target genes such as IFN-beta and ISG15. [less ▲]

Detailed reference viewed: 31 (6 ULg)
See detailidentification of new parterns of the NOD2 protein
Lecat, Aurore ULg; Di Valentin, Emmanuel ULg; Fillet, Marianne ULg et al

Poster (2011, January 27)

Detailed reference viewed: 23 (11 ULg)
See detailRole of MDC1 in NF-kappaB activation by DNA double-strand breaks.
Sabatel, Hélène; Piette, Jacques ULg; Habraken, Yvette ULg

Poster (2011, January 25)

Detailed reference viewed: 7 (0 ULg)
See detailStudy of the combined effect of 5-ALA-based photodynamic therapy and NF-kappaB inhibition on human glioblastoma cell survival
Coupienne, Isabelle ULg; Fettweis, Grégory ULg; Piette, Jacques ULg

Poster (2011, January)

Glioblastoma constitute the most frequent and deadliest type of brain tumors in human adults. They are very resistant to all current therapies and are associated with a huge rate of recurrence. In most ... [more ▼]

Glioblastoma constitute the most frequent and deadliest type of brain tumors in human adults. They are very resistant to all current therapies and are associated with a huge rate of recurrence. In most cases, this type of tumor is characterized by a constitutive activation of the nuclear factor-kappaB (NF-kappaB). This factor is known to be a key regulator of various physiological processes such as inflammation, immune response, cell growth or apoptosis. In the present study, we explored the role of NF-kappaB activation in the sensitivity of human glioblastoma cells to a treatment by 5-aminolevulinic acid (5-ALA)–based photodynamic therapy (PDT). Our results show that inhibition of NF-kappaB improves glioblastoma cell death in response to 5-ALA-PDT. We then studied the molecular mechanisms underlying the cell death induced by PDT combined or not with NF-kappaB inhibition. We found that PDT mainly induced necrosis in glioblastoma cells and NF-kappaB was found to have anti-necrotic functions in this context. In the second part of this study, we examined the role of the kinase RIP3, recently identified as a key effector of the necrotic pathway, in 5-ALA-PDT-induced necrosis and studied whether NF-kappaB interfered in RIP3-dependent necrosis induction. [less ▲]

Detailed reference viewed: 11 (0 ULg)
Full Text
Peer Reviewed
See detailPhotodynamic therapy of cancer: an update.
Agostinis, Patrizia; Berg, Kristian; Cengel, Keith A et al

in CA : A Cancer Journal for Clinicians (2011), 61(4), 250-81

Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of ... [more ▼]

Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. [less ▲]

Detailed reference viewed: 93 (12 ULg)
Full Text
Peer Reviewed
See detailInflammatory signatures for eosinophilic versus neutrophilic allergic pulmonary inflammation reveal critical regulatory checkpoints.
Bogaert, P.; Naessens, T.; De Koker, S. et al

in American Journal of Physiology - Lung Cellular and Molecular Physiology (2011), sous presse

Contrarily to the Th-2-bias and eosinophil-dominated bronchial inflammation encountered in most asthmatics, other patients may exhibit neutrophil-predominant asthma sub-phenotypes along with Th-1 and Th ... [more ▼]

Contrarily to the Th-2-bias and eosinophil-dominated bronchial inflammation encountered in most asthmatics, other patients may exhibit neutrophil-predominant asthma sub-phenotypes along with Th-1 and Th-17 cells. However, the etiology of many neutrophil-dominated asthma sub-phenotypes remains ill-understood, in part due to a lack of appropriate experimental models. To better understand the distinct immune-pathological features of eosinophilic versus neutrophilic asthma types, we developed an Ovalbumin (OVA)-based mouse model of neutrophil-dominated allergic pulmonary inflammation. Consequently, we probed for particular inflammatory signatures and checkpoints underlying the immune-pathology in this new model as well as in a conventional, eosinophil-dominated asthma model. Briefly, mice were OVA-sensitized using either aluminium hydroxide (alum) or Complete Freund's (CFA)-adjuvants followed by OVA aerosol challenge. T-cell, granulocyte and inflammatory mediator profiles were determined along with alveolar macrophage genome-wide transcriptome profiling. In contrast to the Th-2-dominated phenotype provoked by alum, OVA/CFA-adjuvant-based sensitization followed by allergen challenge elicited a pulmonary inflammation that was poorly controlled by dexamethasone, and in which Th-1 and Th-17 cells additionally participated. Analysis of the overall pulmonary and alveolar macrophage inflammatory mediator profiles revealed remarkable similarities between both models. Nevertheless, we observed pronounced differences in the IL-12/IFN-γ axis and its control by IL-18 and IL-18 Binding Protein (BP), but also in macrophage arachidonic acid metabolism and expression of T-cell instructive ligands. These differential signatures, superimposed onto a generic inflammatory signature, denote distinctive inflammatory checkpoints potentially involved in orchestrating neutrophil-dominated asthma. Key words: neutrophil-predominant asthma, allergic inflammation, alveolar macrophage, transcriptome, mouse models. [less ▲]

Detailed reference viewed: 78 (13 ULg)
Peer Reviewed
See detailThe hidden function of NIK (NF-κB-Inducing Kinase) in cell death
Boutaffala, Layla; Bertrand, Mathieu; Remouchamps, Caroline ULg et al

Conference (2011)

Detailed reference viewed: 23 (5 ULg)
Full Text
Peer Reviewed
See detail5-ALA-PDT induces RIP3-dependent necrosis in glioblastoma
Coupienne, Isabelle ULg; Fettweis, Grégory ULg; Rubio-Romero, Noemi ULg et al

in Photochemical & Photobiological Sciences (2011)

Glioblastoma constitute the most frequent and deadliest brain tumors of astrocytic origin. They are resistant to all current therapies and are associated with a high rate of recurrence. Glioblastoma were ... [more ▼]

Glioblastoma constitute the most frequent and deadliest brain tumors of astrocytic origin. They are resistant to all current therapies and are associated with a high rate of recurrence. Glioblastoma were previously shown to respond to treatments by 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT) mainly by activating a necrotic type of cell death. The receptor-interacting protein 3 (RIP3) has recently been outlined as a key mediator of this caspase-independent form of programmed cell death. In the present study, we analyzed the necrotic mechanism induced by 5-ALA-PDT in human glioblastoma cells and explored the role of RIP3 in this context. Our results show that PDT-induced necrosis is dependent on RIP3, which forms aggregates and colocalizes with RIP1 following photosensitization. We demonstrate that PDT-mediated singlet oxygen production is the cause of RIP3-dependent necrotic pathway activation. We also prove that PDT induces the formation of a pro-necrotic complex containing RIP3 and RIP1 but lacking caspase-8 and FADD, two proteins usually part of the necrosome when TNF-α is used as a stimulus. Thus, we hypothesize that PDT might lead to the formation of a different necrosome whose components, besides RIP1 and RIP3, are still unknown. In most cases, glioblastoma are characterized by a constitutive activation of NF-κB. This factor is a key regulator of various processes, such as inflammation, immune response, cell growth or apoptosis. Its inhibition was shown to further sensitize glioblastoma cells to PDT-induced necrosis, however, no difference in RIP3 upshift or aggregation could be observed when NF-κB was inhibited. [less ▲]

Detailed reference viewed: 25 (5 ULg)
See detailNOD2 interactome
Lecat, Aurore ULg; Di Valentin, Emmanuel ULg; Fillet, Marianne ULg et al

Poster (2010, January 28)

Detailed reference viewed: 25 (10 ULg)