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See detailViral induction of Zac1b through TLR3- and IRF3-dependent pathways
Warzée, Barbara ULg; Mesnil, Claire ULg; Hober, D. et al

in Molecular Immunology (2010), 48(1-3), 119-127

Zinc finger protein regulator of apoptosis and cell cycle arrest (Zac1) is a transcription factor able to induce apoptosis or cell cycle arrest through independent pathways. In spite of the important ... [more ▼]

Zinc finger protein regulator of apoptosis and cell cycle arrest (Zac1) is a transcription factor able to induce apoptosis or cell cycle arrest through independent pathways. In spite of the important potential functions attributed to Zac1, little is known of its physiological regulation and biological function. We discovered that variant Zac1b was expressed in murine embryonic fibroblasts (MEFs) treated with polyriboinosinic polyribocytidylic acid [poly(I:C)], a synthetic double-stranded RNA. This regulation occurred mainly through Toll-Like Receptor 3 (TLR3)- and Interferon Regulatory Factor 3 (IRF3)-dependent pathways. As TLR3 and IRF3 are central activators of antiviral immunity, we hypothesized that Zac1 may be implicated in antiviral responses. In line with this notion, we observed that Zac1b was expressed in MEFs infected with Encephalomyocarditis virus (EMCV). We also observed that Zac1-deficient MEFs were less sensitive to EMCV-induced cell death than wild-type MEFs. However, Zac1 gene inactivation had no effect on the survival of mice infected with EMCV. In conclusion, this study describes for the first time a transcriptional regulation of Zac1b, induced by synthetic dsRNA and RNA viruses, the functional significance of which remains to be further investigated. [less ▲]

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See detailThe use of an adapted model allows contributing to the “Reduction” of mice used in experimental protocols: the case of the apoE–deficient (apo E-/-) mice in a model of atherosclerosis control
Cherdon, Céline ULg; Rolin, Stéphanie; de Leval, Laurence ULg et al

Poster (2009, December 01)

Atherosclerosis is a chronic vascular disease whose development is influenced by several mediators 1. Among them, the prostanoids large family lipids generated from the metabolism of arachidonic acid by ... [more ▼]

Atherosclerosis is a chronic vascular disease whose development is influenced by several mediators 1. Among them, the prostanoids large family lipids generated from the metabolism of arachidonic acid by the action of COX includes various types of PGs and thromboxane. Thromboxane A2 and PGI2 are present in abnormally elevated concentration in atherosclerosis 2-3. To exert its effects TXA2 and its precursor PGH2 act at a specific receptor termed TP receptor 4. As a result, TXA2 synthase inhibitors and TP antagonists have been developed to reduce and to prevent TXA2 production and actions, respectively. The present study was undertaken in order to investigate whether BM-573, an original sulfonylurea derivate synthesized in our lab 5, and aspirin would be effective in preventing the progression of atherosclerosis in an apo E deficient mouse model. [less ▲]

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See detailLe PRP (Platelet-Rich Plasma) peut-il favoriser la régénération tendineuse ?
Kaux, Jean-François ULg; Drion, Pierre ULg; Pascon, Frédéric ULg et al

in Annales de Réadaptation et de Médecine Physique (2009, October), 52(Sup. 1), 109-110

Introduction : Certaines tendinopathies (l’épicondylite, la tendinopathie rotulienne supérieure ou encore la tendinopathie d’Achille) demeurent rebelles malgré un traitement « classique » bien conduit ... [more ▼]

Introduction : Certaines tendinopathies (l’épicondylite, la tendinopathie rotulienne supérieure ou encore la tendinopathie d’Achille) demeurent rebelles malgré un traitement « classique » bien conduit : repos, orthèse, AINS, électrothérapie, kinésithérapie, infiltrations de corticoïdes, ondes de choc... Certains travaux, essentiellement in vitro, soulignent les potentialités réparatrices des plaquettes qui présentent la capacité d’accélérer la cicatrisation de différents tissus : os, muscles et tendons. Objectifs : Le but de notre étude préliminaire est d’objectiver l’effet « accélérateur » sur la réparation tendineuse suite à l’emploi d’injection de plasma enrichi en plaquettes (platelet-rich plasma ou PRP) car cette technique pourrait représenter une thérapeutique d’avenir en médecine physique et en traumatologie du sport. Méthodes : Nous avons sectionné et réalisé un défect de 5mm dans le tendon d’Achille de rats (N = 12). Quatre rats ont bénéficié d’une injection in loco de PRP et remis en liberté comme les autres dans leur cage. Trois rats (2 sans PRP et 1 avec PRP) sont euthanasiés à J5, J10, J20 et J30 et le tendon d’Achille en cours de régénération est disséqué et prélevé. Une étude biomécanique de traction jusqu’à rupture est réalisé à l’aide de « Cryo-jaw ». Résultats : L’analyse des résultats montre que la force développée pour obtenir la rupture tendineuse doit être plus importante pour les tendons ayant bénéficié d’une injection de PRP et ce dès J5. Discussion – Conclusion : Cette série préliminaire permet de montrer que les injections de PRP permettent une accélération de la cicatrisation tendineuse et une augmentation des valeurs de résistances à la traction. Une étude avec un plus grand nombre de sujets est en cours. [less ▲]

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See detailMalignant catarrhal fever induced by alcelaphine herpesvirus 1 is associated with proliferation of CD8+ T cells supporting a latent infection
Dewals, Benjamin G ULg; Boudry, Christel; Farnir, Frédéric ULg et al

Poster (2009, September 11)

Alcelaphine herpesvirus 1 (AlHV 1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD MCF) when cross species transmitted to a variety of susceptible species of the Artiodactyla ... [more ▼]

Alcelaphine herpesvirus 1 (AlHV 1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD MCF) when cross species transmitted to a variety of susceptible species of the Artiodactyla order. Experimentally, WD-MCF can be induced in rabbits. The lesions observed are very similar to those described in natural host species. Here, we used the rabbit model and in vivo 5-Bromo-2’-Deoxyuridine (BrdU) incorporation to study WD-MCF pathogenesis. The results obtained can be summarized as follows. (i) AlHV-1 infection induces CD8+ T cell proliferation detectable as early as 15 days post-inoculation. (ii) While the viral load in peripheral blood mononuclear cells remains below the detection level during most of the incubation period, it increases drastically few days before death. At that time, at least 10% of CD8+ cells carry the viral genome; while CD11b+, IgM+ and CD4+ cells do not. (iii) RT-PCR analyses of mononuclear cells isolated from the spleen and the popliteal lymph node of infected rabbits revealed no expression of ORF25 and ORF9, low or no expression of ORF50, and high or no expression of ORF73. Based on these data, we propose a new model for the pathogenesis of WD-MCF. This model relies on proliferation of infected CD8+ cells supporting a predominantly latent infection. [less ▲]

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See detailLe bm-573, un antagoniste original du récepteur au thromboxane a2, réduit le développement des lésions athéromateuses chez des souris déficientes en apolipoprotéine e (apo e-/-) contrairement a l’aspirine.
Cherdon, Céline ULg; Rolin, Stéphanie; Ooms, Annie ULg et al

(2009, May 28)

Afin d’examiner l'efficacité de l’aspirine et du BM-573 dans l'athérogenèse, des souris apo E-/- femelles ont été traitées durant 10 et 20 semaines avec le BM-573 (10mg/kg/j), l’aspirine (30mg/kg/j) ou un ... [more ▼]

Afin d’examiner l'efficacité de l’aspirine et du BM-573 dans l'athérogenèse, des souris apo E-/- femelles ont été traitées durant 10 et 20 semaines avec le BM-573 (10mg/kg/j), l’aspirine (30mg/kg/j) ou un placébo. Au cours de cette expérience, aucune modification du poids corporel ou de la cholestérolémie n’a été observée. Par contre, le traitement des animaux par le BM-573, a eu pour effet de diminuer les lésions athéromateuses de manière significative tandis que l’aspirine a été sans effet sur ce paramètre. Ces données ont été confirmées par des analyses histopathologiques et biochimiques. Ces résultats confirment que l'antagonisme sélectif des récepteurs TP associé à une inhibition de la thromboxane synthétase réduit significativement les lésions athéromateuses chez les souris apo E-/-. Le BM-573 est, par conséquent, un agent thérapeutique potentiel pour la prévention de l'athérosclérose. [less ▲]

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See detailMalignant catarrhal fever induced by alcelaphine herpesvirus 1 is associated with proliferation of CD8+ T cells supporting a latent infection
Dewals, Benjamin G ULg; Boudry, Christel; Farnir, Frédéric ULg et al

Conference (2009, April)

Alcelaphine herpesvirus 1 (AlHV 1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD MCF) when cross species transmitted to a variety of susceptible species of the Artiodactyla ... [more ▼]

Alcelaphine herpesvirus 1 (AlHV 1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD MCF) when cross species transmitted to a variety of susceptible species of the Artiodactyla order. Experimentally, WD-MCF can be induced in rabbits. The lesions observed are very similar to those described in natural host species. Here, we used the rabbit model and in vivo 5-Bromo-2’-Deoxyuridine (BrdU) incorporation to study WD-MCF pathogenesis. The results obtained can be summarized as follows. (i) AlHV-1 infection induces CD8+ T cell proliferation detectable as early as 15 days post-inoculation. (ii) While the viral load in peripheral blood mononuclear cells remains below the detection level during most of the incubation period, it increases drastically few days before death. At that time, at least 10% of CD8+ cells carry the viral genome; while CD11b+, IgM+ and CD4+ cells do not. (iii) RT-PCR analyses of mononuclear cells isolated from the spleen and the popliteal lymph node of infected rabbits revealed no expression of ORF25 and ORF9, low or no expression of ORF50, and high or no expression of ORF73. Based on these data, we propose a new model for the pathogenesis of WD-MCF. This model relies on proliferation of infected CD8+ cells supporting a predominantly latent infection. [less ▲]

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See detailA crucial role forlung interstitial macrophages in preventing airway allergy
Bedoret, Denis; Wallemacq, Hugues ULg; Marichal, Thomas ULg et al

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

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See detailLung interstitial macrophages prevent the development of respiratory allergy
Bedoret, D.; Wallemacq, Hugues ULg; Marichal, Thomas ULg et al

in Proceedings of The Keystone Symposia: Allergy and Asthma. Keystone, Colorado, USA (2009)

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See detailReconstitution du système immunitaire après allogreffe de cellules souches hématopoïétiques
Castermans, Emilie ULg; Hannon, Muriel ULg; Drion, Pierre ULg et al

in Revue Médicale de Liège (2009), 64(S1), 2-8

Allogeneic hematopoietic stem cell transplantation (alloHCT) is frequently used as treatment for patients with hematological malignancies. Its efficacy depends in part on the destruction of recipient ... [more ▼]

Allogeneic hematopoietic stem cell transplantation (alloHCT) is frequently used as treatment for patients with hematological malignancies. Its efficacy depends in part on the destruction of recipient tumors cells by donor immune cells contained in the graft (graft-versus-tumor effects), underlying the interest of stydying donor immune recovery after alloHCT. Further, donor immune cells play an important role in the prevention and treatment of infections after allHCT, and are the cause of graft-versus-host disease (GVHD). This article reviews the mechanisms of immune recovery after allogeneic hematopoietic cell transplantation (alloHCT), as well as techniques currently used to monitor immune function following allHCT. [less ▲]

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See detailInterstitial macrophages are essential for maintaining immune homeostasis in the lung
Bedoret, Denis; Wallemacq, Hugues ULg; Marichal, Thomas ULg et al

in Proceedings of The Allergy & Asthma Symposium: Bridging Innate and Adaptive Immunity (2009)

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See detailLung interstitial macrophages alter dendritic cell functions to prevent airway allergy in mice
Bedoret, Denis ULg; Wallemacq, Hugues ULg; Marichal, Thomas ULg et al

in Journal of Clinical Investigation (2009), 119(12), 3723-38

The respiratory tract is continuously exposed to both innocuous airborne antigens and immunostimulatory molecules of microbial origin, such as LPS. At low concentrations, airborne LPS can induce a lung DC ... [more ▼]

The respiratory tract is continuously exposed to both innocuous airborne antigens and immunostimulatory molecules of microbial origin, such as LPS. At low concentrations, airborne LPS can induce a lung DC-driven Th2 cell response to harmless inhaled antigens, thereby promoting allergic asthma. However, only a small fraction of people exposed to environmental LPS develop allergic asthma. What prevents most people from mounting a lung DC-driven Th2 response upon exposure to LPS is not understood. Here we have shown that lung interstitial macrophages (IMs), a cell population with no previously described in vivo function, prevent induction of a Th2 response in mice challenged with LPS and an experimental harmless airborne antigen. IMs, but not alveolar macrophages, were found to produce high levels of IL-10 and to inhibit LPS-induced maturation and migration of DCs loaded with the experimental harmless airborne antigen in an IL-10-dependent manner. We further demonstrated that specific in vivo elimination of IMs led to overt asthmatic reactions to innocuous airborne antigens inhaled with low doses of LPS. This study has revealed a crucial role for IMs in maintaining immune homeostasis in the respiratory tract and provides an explanation for the paradox that although airborne LPS has the ability to promote the induction of Th2 responses by lung DCs, it does not provoke airway allergy under normal conditions. [less ▲]

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See detailStudy of thromboxane modulators in a murine model of atherosclerosis
Cherdon, Céline ULg; Rolin, Stéphanie; de Leval, Laurence ULg et al

(2008, July 04)

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See detailLung interstitial macrophages prevent lipopolysaccharide-triggered T helper type 2 responses to harmless inhaled antigens
Bedoret, D.; Wallemacq, Hugues ULg; Marichal, Thomas ULg et al

in Proceedings of the Annual BIS-meeting (2008)

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See detailCloning of the koi herpesvirus genome as an infectious bacterial artificial chromosome demonstrates that disruption of the thymidine kinase locus induces partial attenuation in Cyprinus carpio koi.
Costes, Bérénice ULg; Fournier, Guillaume ULg; Michel, Benjamin ULg et al

in Journal of Virology (2008), 82(10), 4955-4964

Koi herpesvirus (KHV) is the causative agent of a lethal disease in koi and common carp. In the present study, we describe the cloning of the KHV genome as a stable and infectious bacterial artificial ... [more ▼]

Koi herpesvirus (KHV) is the causative agent of a lethal disease in koi and common carp. In the present study, we describe the cloning of the KHV genome as a stable and infectious bacterial artificial chromosome (BAC) clone that can be used to produce KHV recombinant strains. This goal was achieved by the insertion of a loxP-flanked BAC cassette into the thymidine kinase (TK) locus. This insertion led to a BAC plasmid that was stably maintained in bacteria and was able to regenerate virions when permissive cells were transfected with the plasmid. Reconstituted virions free of the BAC cassette but carrying a disrupted TK locus (the FL BAC-excised strain) were produced by the transfection of Cre recombinase-expressing cells with the BAC. Similarly, virions with a wild-type revertant TK sequence (the FL BAC revertant strain) were produced by the cotransfection of cells with the BAC and a DNA fragment encoding the wild-type TK sequence. Reconstituted recombinant viruses were compared to the wild-type parental virus in vitro and in vivo. The FL BAC revertant strain and the FL BAC-excised strain replicated comparably to the parental FL strain. The FL BAC revertant strain induced KHV infection in koi carp that was indistinguishable from that induced by the parental strain, while the FL BAC-excised strain exhibited a partially attenuated phenotype. Finally, the usefulness of the KHV BAC for recombination studies was demonstrated by the production of an ORF16-deleted strain by using prokaryotic recombination technology. The availability of the KHV BAC is an important advance that will allow the study of viral genes involved in KHV pathogenesis, as well as the production of attenuated recombinant candidate vaccines. [less ▲]

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See detailMalignant catarrhal fever induced by alcelaphine herpesvirus 1 is associated with proliferation of CD8+ T cells supporting a latent infection.
Dewals, Benjamin G ULg; Boudry, Christel ULg; Farnir, Frédéric ULg et al

in PLoS ONE (2008), 3(2), 1627

Alcelaphine herpesvirus 1 (AlHV-1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD-MCF) when cross-species transmitted to a variety of susceptible species of the Artiodactyla ... [more ▼]

Alcelaphine herpesvirus 1 (AlHV-1), carried by wildebeest asymptomatically, causes malignant catarrhal fever (WD-MCF) when cross-species transmitted to a variety of susceptible species of the Artiodactyla order. Experimentally, WD-MCF can be induced in rabbits. The lesions observed are very similar to those described in natural host species. Here, we used the rabbit model and in vivo 5-Bromo-29-Deoxyuridine (BrdU) incorporation to study WD-MCF pathogenesis. The results obtained can be summarized as follows. (i) AlHV-1 infection induces CD8+ T cell proliferation detectable as early as 15 days postinoculation. (ii) While the viral load in peripheral blood mononuclear cells remains below the detection level during most of the incubation period, it increases drastically few days before death. At that time, at least 10% of CD8+ cells carry the viral genome; while CD11b+, IgM+ and CD4+ cells do not. (iii) RT-PCR analyses of mononuclear cells isolated from the spleen and the popliteal lymph node of infected rabbits revealed no expression of ORF25 and ORF9, low or no expression of ORF50, and high or no expression of ORF73. Based on these data, we propose a new model for the pathogenesis of WD-MCF. This model relies on proliferation of infected CD8+ cells supporting a predominantly latent infection. [less ▲]

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See detailInfluence of the Ixodes ricinus tick blood-feeding on the antigen-specific antibody response in vivo.
Menten-Dedoyart, Catherine ULg; Couvreur, B.; Thellin, Olivier ULg et al

in Vaccine (2008), 26(52), 6956-64

The blood meal of hard ticks such as Ixodes ricinus lasts several days. This is made possible by tick salivary factors that inhibit inflammation, haemostasis and the host immune response. We assessed the ... [more ▼]

The blood meal of hard ticks such as Ixodes ricinus lasts several days. This is made possible by tick salivary factors that inhibit inflammation, haemostasis and the host immune response. We assessed the latter on a model of immune response in vivo. A significant reduction of specific IgM and IgG levels was observed in BALB/c mice infested 5 days before injection with bovine serum albumin (BSA) and QuilA but not in mice infested 5 days after the immunization. This effect was not observed in mock-infested mice and could not be attributed to the use of anesthetics. The antibody response was not merely delayed and the Th(1)/Th(2) balance appeared not altered. T-dependent zones and germinal centers in lymph nodes draining the tick bite site showed no apparent morphological alterations or shift in T cell subpopulations. However, the spleens of tick-infested mice had also an enlarged red pulp, indicating an increased extramedullary haematopoietic activity. [less ▲]

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See detailIn vivo administration of a PKA type I inhibitor (Rp-8-Br-cAMPS) restores T-cell responses in retrovirus-infected mice
Nayjib, Btissam ULg; Zeddou, Mustapha ULg; Drion, Pierre ULg et al

in Open Immunol journal (2008), 1

Murine AIDS (MAIDS) is caused by infection with the murine leukemia retrovirus RadLV-Rs and is characterized by T-cell anergy and severe immunodeficiency with increased susceptibilty to several ... [more ▼]

Murine AIDS (MAIDS) is caused by infection with the murine leukemia retrovirus RadLV-Rs and is characterized by T-cell anergy and severe immunodeficiency with increased susceptibilty to several experimental opportunistic infections as observed in HIV infection. T cell anergy is associated with an increase of intracellular cAMP level, triggering a multistep pathway involving activation of PKA type I and resulting in inhibition of proximal TCR signaling. We have reviously demonstrated that blocking PKA type I using the selective inhibitor Rp-8-Br-cAMPS, restores T-cell function in vitro in MAIDS as well as in HIV infection. In the present report, we investigated the effect of parenteral administration of Rp-8-Br-cAMPS in mice with MAIDS. We show that the compound is not toxic and partially restores the ex vivo proliferative responses to anti-CD3 mAb, but that it has no effect on the lymphadenopathy and splenomegaly characterizing the MAIDS syndrome. [less ▲]

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See detailEvolution of anti-eCG antibodies in response to eCG doses and number of injections. Relation with rabbit does productivity
Theau-Clément, M.; Lebas, F.; Beckers, J. F. et al

in Animal (2008), 2(5), 746-751

The aim of this experiment was to study the kinetics of anti-eCG (equine chorionic gonadotrophin) antibodies in relation to eCG dose (8 or 25 IU) and number of injections (n = 11) in comparison with a ... [more ▼]

The aim of this experiment was to study the kinetics of anti-eCG (equine chorionic gonadotrophin) antibodies in relation to eCG dose (8 or 25 IU) and number of injections (n = 11) in comparison with a control group (no injection), and to relate antibody production to sexual receptivity and productivity of rabbit does. In all, 124 lactating primiparous rabbit does were inseminated every 35 days for a year. Just before eCG injection (48 h before insemination), blood samples were collected from all the does to assay anti-eCG antibodies. The anti-eCG antibody binding rate, regardless of the injected dose, shows that none of the does developed detectable anti-eCG antibodies before the 7th injection. The level of detectable anti-eCG antibodies began to show an increase at the 7th injection and was significant only for the 25 IU dose at the 11th injection. At the end of the experiment, 15% and 39% of does treated with 8 and 25 IU, respectively, developed immunity to eCG (binding rate >6%: higher binding rate of the control group). Consequently, the immune response depends on the eCG dose and on the number of injections. Moreover, productivity of does estimated from the number of weaned rabbits produced per insemination is not influenced by the level of eCG antibodies (7.0 and 6.9 for binding rate <6% and binding rate 6%, respectively). Only 19 inseminations (n = 6 and n = 13 for 8 and 25 IU, respectively) were made on hyperimmune does. Consequently, the immune response to eCG seems to be marginal for rabbit does. Moreover, under the described experimental conditions, reproductive performances of hyperimmune does were not affected [less ▲]

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See detailRépertoire commenté des Médicaments à Usage vétérinaire
Drion, Pierre ULg

in Livre Substances hormonales. Partim Hormones. Médicaments du système hormonal – hormones sexuelles et autres médicaments du système reproducteur (2008)

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See detailBm-573, an original thromboxane receptor antagonist, reduces development of atherosclerosis in apoe–deficient (apo e-/-) mice
Cherdon, Céline ULg; Rolin, Stéphanie; Hanson, Julien ULg et al

Poster (2007, October 11)

To test the efficacy of BM-573 in atherogenesis, the effect of 10 weeks of treatment with BM573 (10 mg/l) on early aortic atherosclerotic lesions of apo E deficient mice was assessed. These mice were fed ... [more ▼]

To test the efficacy of BM-573 in atherogenesis, the effect of 10 weeks of treatment with BM573 (10 mg/l) on early aortic atherosclerotic lesions of apo E deficient mice was assessed. These mice were fed with chow diet, with spontaneous increase of total plasma cholesterol and triglycerides. In this experiment, while BM-573 did not affect body weight, it significantly decreases early atherogenesis lesions confirmed by macroscopic, microscopic and biochemical analysis. These results confirm that selective antagonism of TP receptor is effective in reducing atherosclerotic lesion in apo E deficient mice. Consequently, BM-573 could be a potential drug for prevention of atherosclerosis [less ▲]

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