References of "Pirottin, Dimitri"
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See detailExpression microarray as a tool to identify candidate blood biomarkers in horses suffering from inflammatory airway disease
Ramery, Eve ULg; Fraipont, Audrey ULg; Art, Tatiana ULg et al

in Veterinary Clinical Pathology (in press)

Background: Inflammatory airway disease (IAD) affects performance and well-being in horses. Diagnosis is primarily reached by bronchoalveolar lavage (BAL) cytology but this is invasive and requires ... [more ▼]

Background: Inflammatory airway disease (IAD) affects performance and well-being in horses. Diagnosis is primarily reached by bronchoalveolar lavage (BAL) cytology but this is invasive and requires sedation. Objectives: The purpose of this study was to identify candidate blood biomarkers of IAD using species-specific expression microarrays. Methods: Horse Gene Expression Microarrays were used to investigate global mRNA expression in circulating leukocytes from healthy and IAD-affected standardbreds and endurance horses. Results: Nine genes were significantly differentially regulated in standardbreds and 61 in endurance horses (P < 0.001). These genes were mainly related to inflammation (eg. ALOX15B, PLA2G12B and PENK), oxidant/antioxidant balance (eg. DUOXA2 and GSTO1-1) and stress (eg. V1aR, GRLF1, Homer-2 and MAOB). DUOXA2, ALOX15B, PLA2G12B, MAOB and GRLF1 variations of expression were further validated by RT-qPCR. The deregulation of the oxidant/antioxidant balance was demonstrated at the protein level by an increase of glutathione peroxidase (GPx) activity in heparinised whole blood of IAD-affected standardbreds (P = 0.0025) and endurance horses (P = 0.0028). There was good correlation (r = 0.7354) between BAL neutrophil percentage and whole blood GPx activity in all horses. Conclusions: There is accumulating evidence that, even when systemic clinical signs are not evident, circulating leukocyte gene expression can reflect responses of other tissues, leading to potential diagnostic applications in the future. Although not specific for IAD, whole blood GPx activity appears to reflect BAL neutrophil percentage. This finding should be further assessed by testing a larger number of horses. [less ▲]

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See detailExercise modifies the innate immune response in equine bronchial epithelial cells
Frellstedt, Linda ULg; Gosset, Philippe; Pirottin, Dimitri ULg et al

in Proceedings of the 3rd Scientific Meeting of the Faculty of Veterinary Medicine (University of Liege - Belgium) (2013)

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See detailExperimental model of equine alveolar macrophage stimulation with TLR ligands.
Waldschmidt, Ingrid; Pirottin, Dimitri ULg; Art, Tatiana ULg et al

in Veterinary Immunology and Immunopathology (2013), 155(1-2), 30-37

Pulmonary diseases are common in horses and have a major economic impact on the equine industry. Some of them could be associated with an inadequate immune response in the lung, but methods to evaluate ... [more ▼]

Pulmonary diseases are common in horses and have a major economic impact on the equine industry. Some of them could be associated with an inadequate immune response in the lung, but methods to evaluate this response in horses are lacking. The aim of this study was to develop and validate an experimental model that could be applied in several physiological and pathological conditions to assess the innate immune response of equine pulmonary cells. Equine alveolar macrophages (AMs) obtained from bronchoalveolar lavages were isolated from other cells by adhesion. TLR2, 3, and 4 expression in AMs was studied and their responses to commercial ligands (respectively FSL-1, Poly(I:C), and LPS) were evaluated after determination of the appropriate dose and time of incubation. TLR responses were assessed by measuring cytokine production using (1) gene expression of TNFalpha, IFNbeta, Il-1beta, and IFNalpha by qPCR (indirect method); and (2) cytokine production for TNFalpha and IFNbeta by ELISA (direct method). TLR 2, 3, and 4 were expressed by AMs. TLR 2 stimulation with 10ng/mL of FSL-1 during 3h significantly increased IL-1beta and TNFalpha gene expression. TLR 3 stimulation with 1000ng/mL of Poly(I:C) during 1h increased IFNbeta, IFNalpha, Il-1beta and TNFalpha expression. TLR 4 stimulation with 100ng/mL of LPS during 3h increased TNFalpha, IFNbeta, and Il-1beta expression. Results obtained by ELISA quantification of TNFalpha and IFNbeta produced by AMs following stimulation during 6h were similar: FSL-1 increased TNFalpha production but not IFNbeta, Poly(I:C) and LPS increased production of IFNbeta and TNFalpha. In conclusion, pulmonary innate immunity of horses can be assessed ex vivo by measuring cytokine production following stimulation of AMs with TLR agonists. This experimental model could be applied under several conditions especially to improve the understanding of equine respiratory disease pathogenesis, and to suggest novel therapeutic opportunities. [less ▲]

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See detailInvestigation of the effect of exercise on the innate immunity in horses
Frellstedt, Linda ULg; Gosset, Philippe; Desmet, Christophe ULg et al

Poster (2012, October 19)

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See detailIncreased hypoxia-inducible factor 1alpha expression in lung cells of horses with recurrent airway obstruction.
Toussaint, Marie ULg; Fievez, Laurence ULg; Desmet, Christophe ULg et al

in BMC Veterinary Research (2012), 8(1), 64

ABSTRACT: BACKGROUND: Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological ... [more ▼]

ABSTRACT: BACKGROUND: Recurrent airway obstruction (RAO, also known as equine heaves) is an inflammatory condition caused by exposure of susceptible horses to organic dusts in hay. The immunological processes responsible for the development and the persistence of airway inflammation are still largely unknown. Hypoxia-inducible factor (Hif) is mainly known as a major regulator of energy homeostasis and cellular adaptation to hypoxia. More recently however, Hif also emerged as an essential regulator of innate immune responses. Here, we aimed at investigating the potential involvement of Hif1-alpha in myeloid cells in horse with recurrent airway obstruction. RESULTS: In vitro, we observed that Hif is expressed in equine myeloid cells after hay dust stimulation and regulates genes such as tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGF-A). We further showed in vivo that airway challenge with hay dust upregulated Hif1-alpha mRNA expression in myeloid cells from the bronchoalveolar lavage fluid (BALF) of healthy and RAO-affected horses, with a more pronounced effect in cells from RAO-affected horses. Finally, Hif1-alpha mRNA expression in BALF cells from challenged horses correlated positively with lung dysfunction. CONCLUSION: Taken together, our results suggest an important role for Hif1-alpha in myeloid cells during hay dust-induced inflammation in horses with RAO. We therefore propose that future research aiming at functional inactivation of Hif1 in lung myeloid cells could open new therapeutic perspectives for RAO. [less ▲]

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See detailLe microdamier d’expression : un outil performant dans la compréhension de la réponse
Schoeneker, Julie; Art, Tatiana ULg; Pirottin, Dimitri ULg et al

in Annales de Médecine Vétérinaire (2011), 154

Malgré de multiples études, les interrelations entre l’exercice, le stress et la réponse immune sont peu définies. Or, la compréhension de ces interrelations pourrait jouer un rôle très important dans ... [more ▼]

Malgré de multiples études, les interrelations entre l’exercice, le stress et la réponse immune sont peu définies. Or, la compréhension de ces interrelations pourrait jouer un rôle très important dans l’amélioration de la santé et des résultats sportifs des athlètes. En effet, l’exercice peut être reconnu comme un stress. Il induit des modifications de l’équilibre homéostatique qui peuvent à leur tour altérer la réponse immunitaire de l’hôte et donc sa susceptibilité aux maladies. L’adrénaline est la molécule essentielle de tout processus de stress. La technologie des microdamiers, outil majeur d’investigation transcriptomique, permet l’étude de l’expression génique de l’ensemble du génome. Son utilisation devrait donc permettre de mieux caractériser et définir les interrelations entre l’exercice, le stress et la réponse immune. Cette revue recense les interrelations connues entre la réponse immune à un stress adrénergique d’une part et la réponse immune à l’exercice d’autre part. Elle considère en outre la contribution potentielle des microdamiers à une meilleure compréhension des effets d’un stress, et plus particulièrement celui lié à l’exercice, sur l’immunité. [less ▲]

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See detailInvestigation of the innate immunity in the lower respiratory tract in exercising horses
Frellstedt, Linda ULg; Gosset, Philippe; Desmet, Christophe ULg et al

in Proceedings of the 1st Scientific Meeting of the Faculty of Veterinary Medicine (2011)

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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 detailPolymorphic miRNA-target interactions : A Novel Source of Phenotypic Variation
Georges, Michel ULg; Clop, Alex; Marcq, Fabienne ULg et al

in Cold Spring Harbor Symposia on Quantitative Biology (2006, June), 71

Studying the muscular hypertrophy of Texel sheep by forward genetics, we have identified an A-to-G transition in the 3'UTRof the GDF8 gene that reveals an illegitimate target site for microRNAs miR-1 and ... [more ▼]

Studying the muscular hypertrophy of Texel sheep by forward genetics, we have identified an A-to-G transition in the 3'UTRof the GDF8 gene that reveals an illegitimate target site for microRNAs miR-1 and miR-206 that are highly expressed in skeletal muscle. This causes the down-regulation of this muscle-specific chalone and hence contributes to the muscular hypertrophyof Texel sheep. We demonstrate that polymorphisms which alter the content of putative miRNA target sites are commonin human and mice, and provide evidence that both conserved and nonconserved target sites are selectively constrained. Wespeculate that these polymorphisms might be important mediators of phenotypic variation including disease. To facilitatestudies along those lines, we have constructed a database (www.patrocles.org) listing putative polymorphic microRNA–targetinteractions. [less ▲]

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See detailA mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep.
Clop, Alex; Marcq, Fabienne ULg; Takeda, Haruko ULg et al

in Nature Genetics (2006), 38(7), 813-8

Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We ... [more ▼]

Texel sheep are renowned for their exceptional meatiness. To identify the genes underlying this economically important feature, we performed a whole-genome scan in a Romanov x Texel F2 population. We mapped a quantitative trait locus with a major effect on muscle mass to chromosome 2 and subsequently fine-mapped it to a chromosome interval encompassing the myostatin (GDF8) gene. We herein demonstrate that the GDF8 allele of Texel sheep is characterized by a G to A transition in the 3' UTR that creates a target site for mir1 and mir206, microRNAs (miRNAs) that are highly expressed in skeletal muscle. This causes translational inhibition of the myostatin gene and hence contributes to the muscular hypertrophy of Texel sheep. Analysis of SNP databases for humans and mice demonstrates that mutations creating or destroying putative miRNA target sites are abundant and might be important effectors of phenotypic variation. [less ▲]

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See detailTransgenic engineering of male-specific muscular hypertrophy.
Pirottin, Dimitri ULg; Grobet, Luc ULg; Adamantidis, Antoine ULg et al

in Proceedings of the National Academy of Sciences of the United States of America (2005), 102(18), 6413-8

Using a two-step procedure involving insertional gene targeting and recombinase-mediated cassette exchange in ES cells, we have produced two lines of transgenic mice expressing a dominant-negative latency ... [more ▼]

Using a two-step procedure involving insertional gene targeting and recombinase-mediated cassette exchange in ES cells, we have produced two lines of transgenic mice expressing a dominant-negative latency-associated myostatin propeptide under control of the myosin light chain 1F promoter and 1/3 enhancer from the TSPY locus on the Y chromosome. Males of the corresponding lines are characterized by a 5-20% increase in skeletal muscle mass. This experiment demonstrates the feasibility of a more efficient cattle production system combining superior beef production abilities for bulls and dairy abilities for cows. [less ▲]

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See detailPositional cloning and genetic engineering of the myostatin gene causing double muscling in cattle
Pirottin, Dimitri ULg; Grobet, L.; Georges, Michel ULg

in Annales de Médecine Vétérinaire (2005), 149(3), 135-147

Double-muscling in cattle is a generalised hypertrophy of skeletal muscle resulting from a hyperplasia of the myofibers. Using a positional cloning strategy, we have identified the gene underlying double ... [more ▼]

Double-muscling in cattle is a generalised hypertrophy of skeletal muscle resulting from a hyperplasia of the myofibers. Using a positional cloning strategy, we have identified the gene underlying double-muscling, namely myostatin, and causal loss-of-function mutations therein. Myostatin is a novel member of the TGF-beta superfamily of growth and differentiation factors. Using conditional gene targeting in a murine model, we have demonstrated that post-natal muscle specific inactivation of the myostatin gene causes full-blown double muscling. This demonstrates the potential value of myostatin antagonist whether to promote muscle regeneration in patients suffering from muscle wasting disease, or to enhance meat production in livestock species. Finally, by targeting a myostatin transinhibitor on the Y chromosome, we have demonstrated in the mouse the feasibility of a more efficient cattle production system combining superior beef production abilities for bulls and dairy abilities for cows. [less ▲]

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See detailModulating skeletal muscle mass by postnatal, muscle-specific inactivation of the myostatin gene.
Grobet, Luc ULg; Pirottin, Dimitri ULg; Farnir, Frédéric ULg et al

in Genesis (2003), 35(4), 227-38

By using a conditional gene targeting approach exploiting the cre-lox system, we show that postnatal inactivation of the myostatin gene in striated muscle is sufficient to cause a generalized muscular ... [more ▼]

By using a conditional gene targeting approach exploiting the cre-lox system, we show that postnatal inactivation of the myostatin gene in striated muscle is sufficient to cause a generalized muscular hypertrophy of the same magnitude as that observed for constitutive myostatin knockout mice. This formally demonstrates that striated muscle is the production site of functional myostatin and that this member of the TGFbeta family of growth and differentiation factors regulates muscle mass not only during early embryogenesis but throughout development. It indicates that myostatin antagonist could be used to treat muscle wasting and to promote muscle growth in man and animals. [less ▲]

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See detailHigh-Resolution, Human-Bovine Comparative Mapping Based on a Closed Yac Contig Spanning the Bovine Mh Locus
Pirottin, Dimitri ULg; Poncelet, D.; Grobet, Luc ULg et al

in Mammalian Genome : Official Journal of the International Mammalian Genome Society (1999), 10(3), 289-93

A closed YAC contig spanning the mh locus was assembled by STS content mapping with seven microsatellite markers, eight genes or EST, and nine STS corresponding to YAC ends. The contig comprises 27 YACs ... [more ▼]

A closed YAC contig spanning the mh locus was assembled by STS content mapping with seven microsatellite markers, eight genes or EST, and nine STS corresponding to YAC ends. The contig comprises 27 YACs, has an average depth of 4.3 YACs, and spans an estimated 1.2 Mb. A linkage map was constructed based on five of the microsatellite markers anchored to the contig and shown to span 7 cM, yielding a ratio of 160 kb/1 cM for the corresponding chromosome region. Comparative mapping data indicate that the constructed contig spans an evolutionary breakpoint connecting two chromosome segments that are syntenic but not adjacent in the human. Consolidation of human gene order by means of whole genome radiation hybrids and its comparison with the bovine order as inferred from the contig confirm conservation of gene order within segments. [less ▲]

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See detailMolecular Definition of an Allelic Series of Mutations Disrupting the Myostatin Function and Causing Double-Muscling in Cattle
Grobet, Luc ULg; Poncelet, D.; Royo, L. J. et al

in Mammalian Genome : Official Journal of the International Mammalian Genome Society (1998), 9(3), 210-3

We have determined the entire myostatin coding sequence for 32 double-muscled cattle sampled from ten European cattle breeds. Seven DNA sequence polymorphisms were identified, of which five would be ... [more ▼]

We have determined the entire myostatin coding sequence for 32 double-muscled cattle sampled from ten European cattle breeds. Seven DNA sequence polymorphisms were identified, of which five would be predicted to disrupt the function of the protein, one is a conservative amino acid substitution, and one a silent DNA sequence variant. Four additional DNA sequence polymorphisms were identified in myostatin intronic sequences. In all but two breeds, all double-muscled animals were either homozygous or compound heterozygotes for one of the five loss-of-function mutations. The absence of obvious loss-of-function mutations in the coding sequence of the two remaining breeds points either towards additional mutations in unexplored segments of the gene, or towards locus heterogeneity of double-muscling. [less ▲]

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See detailA Deletion in the Bovine Myostatin Gene Causes the Double-Muscled Phenotype in Cattle
Grobet, L.; Martin, L. J.; Poncelet, D. et al

in Nature Genetics (1997), 17(1), 71-74

An exceptional muscle development commonly referred to as 'double-muscled' (Fig. 1) has been seen in several cattle breeds and has attracted considerable attention from beef producers. Double-muscled ... [more ▼]

An exceptional muscle development commonly referred to as 'double-muscled' (Fig. 1) has been seen in several cattle breeds and has attracted considerable attention from beef producers. Double-muscled animals are characterized by an increase in muscle mass of about 20%, due to general skeletal-muscle hyperplasia-that is, an increase in the number of muscle fibers rather than in their individual diameter. Although the hereditary nature of the double-muscled condition was recognized early on, the precise mode of inheritance has remained controversial; monogenic (domainant and recessive), oligogenic and polygenic models have been proposed. In the Belgian Blue cattle breed (BBCB), segregation analysis performed both in experimental crosses and in the outbred population suggested an autosomal recessive inheritance. This was confirmed when the muscular hypertrophy (mh) locus was mapped 3.1 cM from microsatellite TGLA44 on the centromeric end of bovine chromosome 2 (ref. 5). We used a positional candidate approach to demonstrate that a mutation in bovine MSTN, which encodes myostatin, a member of the TGF beta superfamily, is responsible for the double-muscled phenotype. We report an 11-bp deletion in the coding sequence for the bioactive carboxy-terminal domain of the protein causing the muscular hypertrophy observed in Belgian Blue cattle. [less ▲]

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See detailThe ovarian follicle in cow: in vivo growth and in vitro culture
Beckers, Jean-François ULg; Drion, Pierre ULg; Figueiredo, J. R. et al

in Reproduction in Domestic Animals (1996), 31

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