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Your search keyword '"MESH : Fibroblasts"' showing total 14 results
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14 results on '"MESH : Fibroblasts"'

1. Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability

Author

Mireille Melko, Samantha Zongaro, Jozef Gecz, Dominique Douguet, Barbara Bardoni, Céline Verheggen, Mounia Bensaid, Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Montpellier ( UM ), Department of Genetic Medicine Women's and Children's, University of Adelaide, Université Côte d'Azur ( UCA ), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)

Subjects
MESH : Cell Line, MESH : Molecular Sequence Data, MESH: Sequence Homology, Amino Acid, Gene Expression, RNA-binding protein, MESH: Amino Acid Sequence, MESH: Gene Order, Exon, 0302 clinical medicine, MESH : Protein Transport, Genes, Reporter, Transcription (biology), Gene Order, Genetics (clinical), Genetics, 0303 health sciences, MESH : Amino Acid Sequence, MESH : Sequence Alignment, RNA-Binding Proteins, General Medicine, MESH : Genes, Reporter, Phenotype, MESH : Sequence Homology, Amino Acid, DNA-Binding Proteins, Protein Transport, MESH : Fragile X Syndrome, 030220 oncology & carcinogenesis, RNA splicing, MESH : RNA Splicing, MESH : DNA-Binding Proteins, Intranuclear Space, MESH: Fragile X Syndrome, MESH: Protein Transport, MESH: Gene Expression, RNA Splicing, Molecular Sequence Data, MESH : RNA-Binding Proteins, MESH: Sequence Alignment, MESH: Intranuclear Space, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Cell Line, 03 medical and health sciences, MESH : Fibroblasts, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : HeLa Cells, Amino Acid Sequence, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Gene, 030304 developmental biology, MESH: Molecular Sequence Data, MESH: Humans, MESH : Gene Order, Sequence Homology, Amino Acid, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH: Genes, Reporter, MESH : Humans, Alternative splicing, RNA, Fibroblasts, MESH: Cell Line, MESH : Gene Expression, MESH: RNA-Binding Proteins, MESH : Intranuclear Space, MESH: Fibroblasts, Fragile X Syndrome, MESH: HeLa Cells, MESH: RNA Splicing, Sequence Alignment, MESH: DNA-Binding Proteins, HeLa Cells
Abstract

International audience; The AFF (AF4/FMR2) family of genes includes four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. AFF2/FMR2 is silenced in FRAXE intellectual disability, while the other three members have been reported to form fusion genes as a consequence of chromosome translocations with the myeloid/lymphoid or mixed lineage leukemia (MLL) gene in acute lymphoblastic leukemias (ALLs). All AFF proteins are localized in the nucleus and their role as transcriptional activators with a positive action on RNA elongation was primarily studied. We have recently shown that AFF2/FMR2 localizes to nuclear speckles, subnuclear structures considered as storage/modification sites of pre-mRNA splicing factors, and modulates alternative splicing via the interaction with the G-quadruplex RNA-forming structure. We show here that similarly to AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31 localize to nuclear speckles and are able to bind RNA, having a high apparent affinity for the G-quadruplex structure. Interestingly, AFF3/LAF4 and AFF4/AF5q31, like AFF2/FMR2, modulate, in vivo, the splicing efficiency of a mini-gene containing a G-quadruplex structure in one alternatively spliced exon. Furthermore, we observed that the overexpression of AFF2/3/4 interferes with the organization and/or biogenesis of nuclear speckles. These findings fit well with our observation that enlarged nuclear speckles are present in FRAXE fibroblasts. Furthermore, our findings suggest functional redundancy among the AFF family members in the regulation of splicing and transcription. It is possible that other members of the AFF family compensate for the loss of AFF2/FMR2 activity and as such explain the relatively mild to borderline phenotype observed in FRAXE patients.

Published
2011
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2. The Inflammatory Response in Acyl-CoA Oxidase 1 Deficiency (Pseudoneonatal Adrenoleukodystrophy)

Author

Pierre Andreoletti, Stéphane Mandard, Aurore Vluggens, Gérard Lizard, Sander Kersten, Janardan K. Reddy, H. I. El Hajj, Kévin Ragot, Ronald J.A. Wanders, H. R. Waterham, Mustapha Cherkaoui-Malki, Amsterdam Gastroenterology Endocrinology Metabolism, Laboratory Genetic Metabolic Diseases, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique ( Bio-PeroxIL ), Université de Bourgogne ( UB ), Departments of Clinical Chemistry and Pediatrics, University of Amsterdam [Amsterdam] ( UvA ) -Academic Medical Centre, Nutrition, Metabolism and Genomics Group, Wageningen University and Research Centre [Wageningen] ( WUR ), Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ) -Universiteit van Amsterdam ( UvA ), Institut National de la Santé et de la Recherche Médicale, the Conseil Régional de Bourgogne, the Ministère de l'Enseignement Supérieur et de la Recherche, and the Centre National de la Recherche Scientifique., Mandard, Stéphane, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique (Bio-PeroxIL), Université de Bourgogne (UB), University of Amsterdam [Amsterdam] (UvA)-Academic Medical Centre, Wageningen University and Research [Wageningen] (WUR), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), and University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Universiteit van Amsterdam (UvA)

Subjects
MESH: Inflammation, peroxisomal disorders, MESH: Osteopontin, medicine.medical_treatment, MESH : Immunohistochemistry, MESH : Transcriptome, chemokine receptors, Voeding, Metabolisme en Genomica, 0302 clinical medicine, Endocrinology, MESH: Reverse Transcriptase Polymerase Chain Reaction, Acyl-CoA oxidase, multiple-sclerosis lesions, MESH : Osteopontin, MESH : Fatty Acids, Cells, Cultured, Oligonucleotide Array Sequence Analysis, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, Oxidase test, MESH : Gene Expression Regulation, Reverse Transcriptase Polymerase Chain Reaction, Fatty Acids, MESH: Acyl-CoA Oxidase, MESH : Reverse Transcriptase Polymerase Chain Reaction, Peroxisome, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Immunohistochemistry, MESH: Gene Expression Regulation, Metabolism and Genomics, 3. Good health, MESH: Fatty Acids, MESH : Oligonucleotide Array Sequence Analysis, Cytokine, Metabolisme en Genomica, ACOX1, Adrenoleukodystrophy, Nutrition, Metabolism and Genomics, MESH : Acyl-CoA Oxidase, medicine.symptom, Inflammation Mediators, MESH: Cells, Cultured, medicine.medical_specialty, MESH : Interleukin-8, MESH : Interleukin-6, MESH: Inflammation Mediators, Inflammation, Biology, in-vitro, MESH : Interleukin-1, MESH : Inflammation Mediators, 03 medical and health sciences, Voeding, Internal medicine, Peroxisomal disorder, nf-kappa-b, MESH : Cells, Cultured, MESH : Fibroblasts, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, gene, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Nutrition, 030304 developmental biology, VLAG, MESH: Humans, MESH : Inflammation, Interleukin-6, MESH: Transcriptome, Interleukin-8, MESH : Humans, MESH: Interleukin-1, MESH: Immunohistochemistry, Fibroblasts, medicine.disease, MESH: Interleukin-6, MESH: Interleukin-8, Gene Expression Regulation, MESH: Fibroblasts, MESH: Oligonucleotide Array Sequence Analysis, cells, Brief Reports, Osteopontin, microarray analysis, Acyl-CoA Oxidase, Transcriptome, interleukin-1, 030217 neurology & neurosurgery, x-linked adrenoleukodystrophy, Interleukin-1
Abstract

Among several peroxisomal neurodegenerative disorders, the pseudoneonatal adrenoleukodystrophy (P-NALD) is characterized by the acyl-coenzyme A oxidase 1 (ACOX1) deficiency, which leads to the accumulation of very-long-chain fatty acids ( VLCFA) and inflammatory demyelination. However, the components of this inflammatory process in P-NALD remain elusive. In this study, we used transcriptomic profiling and PCR array analyses to explore inflammatory gene expression in patient fibroblasts. Our results show the activation of IL-1 inflammatory pathway accompanied by the increased secretion of two IL-1 target genes, IL-6 and IL-8 cytokines. Human fibroblasts exposed to very-long-chain fatty acids exhibited increased mRNA expression of IL-1 alpha and IL-1 beta cytokines. Furthermore, expression of IL-6 and IL-8 cytokines in patient fibroblasts was down-regulated by MAPK, p38MAPK, and Jun N-terminal kinase inhibitors. Thus, the absence of acyl-coenzyme A oxidase 1 activity in P-NALD fibroblasts triggers an inflammatory process, in which the IL-1 pathway seems to be central. The use of specific kinase inhibitors may permit the modulation of the enhanced inflammatory status. (Endocrinology 153: 2568-2575, 2012)

Published
2012
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3. DCC constrains tumour progression via its dependence receptor activity

Author

Loraine Jarrosson-Wuilleme, Jean-Yves Scoazec, Guillaume Chazot, Marie Castets, Laura Broutier, Yann Molin, Armelle Paquet, Patrick Mehlen, Nicolas Gadot, Laetitia Mazelin, Marie Brevet, Agnès Bernet, Puisieux, Alain, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Anipath, UFR Médecine Lyon-RTH Laennec, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Deleted in Colorectal Cancer, MESH : Mutant Proteins, MESH : Receptors, Cell Surface, Apoptosis, Dependence receptor, law.invention, MESH : Adenocarcinoma, Mice, MESH: Mutant Proteins, 0302 clinical medicine, law, Netrin, MESH : Intestinal Neoplasms, MESH: Animals, MESH: Gene Silencing, Receptor, Cells, Cultured, Cancer, MESH: Receptors, Cell Surface, 0303 health sciences, MESH: Genes, APC, Multidisciplinary, MESH : Tumor Suppressor Proteins, Genomics, Netrin-1, DCC Receptor, 3. Good health, 030220 oncology & carcinogenesis, Caspases, MESH: HEK293 Cells, Disease Progression, MESH: Disease Progression, MESH : Mutation, MESH: Cells, Cultured, Genes, APC, MESH: Mutation, Context (language use), Receptors, Cell Surface, Biology, Adenocarcinoma, MESH : Nerve Growth Factors, 03 medical and health sciences, MESH : Mice, MESH : Cells, Cultured, MESH : Fibroblasts, MESH : Gene Silencing, Intestinal Neoplasms, Genetics, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene silencing, Animals, Humans, MESH: Tumor Suppressor Proteins, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene Silencing, Nerve Growth Factors, MESH: Intestinal Neoplasms, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Humans, MESH: Caspases, MESH: Nerve Growth Factors, Tumor Suppressor Proteins, MESH: Apoptosis, MESH : Humans, fungi, MESH: Adenocarcinoma, MESH : Disease Progression, Fibroblasts, MESH : Disease Models, Animal, MESH : HEK293 Cells, Disease Models, Animal, MESH : Genes, APC, HEK293 Cells, MESH: Fibroblasts, Immunology, Mutation, Cancer research, Suppressor, Mutant Proteins, MESH : Animals, MESH : Caspases, MESH: Disease Models, Animal, MESH : Apoptosis
Abstract

International audience; The role of deleted in colorectal carcinoma (DCC) as a tumour suppressor has been a matter of debate for the past 15 years. DCC gene expression is lost or markedly reduced in the majority of advanced colorectal cancers and, by functioning as a dependence receptor, DCC has been shown to induce apoptosis unless engaged by its ligand, netrin-1 (ref. 2). However, so far no animal model has supported the view that the DCC loss-of-function is causally implicated as predisposing to aggressive cancer development. To investigate the role of DCC-induced apoptosis in the control of tumour progression, here we created a mouse model in which the pro-apoptotic activity of DCC is genetically silenced. Although the loss of DCC-induced apoptosis in this mouse model is not associated with a major disorganization of the intestines, it leads to spontaneous intestinal neoplasia at a relatively low frequency. Loss of DCC-induced apoptosis is also associated with an increase in the number and aggressiveness of intestinal tumours in a predisposing APC mutant context, resulting in the development of highly invasive adenocarcinomas. These results demonstrate that DCC functions as a tumour suppressor via its ability to trigger tumour cell apoptosis.

Published
2012
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4. Biological effects of space radiation on human cells: history, advances and outcomes

Author

Mira Maalouf, Nicolas Foray, Marco Durante, Ciblage thérapeutique en Oncologie ( EA3738 ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon, equipe 2, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), M., Maalouf, Durante, Marco, N., Foray, Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH : Microscopy, Fluorescence, Health, Toxicology and Mutagenesis, MESH: Microscopy, Fluorescence, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Astronauts, Cosmic Radiation, Cytogenetics, DNA Damage, Fibroblast, Heavy Ions, MESH : DNA Damage, 0303 health sciences, Radiation, Individual susceptibility, Low dose, MESH: Relative Biological Effectiveness, MESH: Heavy Ions, Adaptive response, radiation effects, Heavy Ions, History, 3. Good health, MESH : Radiation Dosage, Risk analysis (engineering), 030220 oncology & carcinogenesis, MESH: Astronauts, Astronauts, MESH: History, 20th Century, history, MESH : Cosmic Radiation, MESH: History, 21st Century, MESH : Heavy Ions, MESH: Radiation Dosage, MESH: Cosmic Radiation, MESH: Radiobiology, [SDV.CAN]Life Sciences [q-bio]/Cancer, Nanotechnology, MESH: Space Flight, 20th Century, History, Biology, Low dose irradiation, Radiation Dosage, History, 21st Century, Fluorescence, MESH : Cytogenetics, Cytogenetics, 03 medical and health sciences, MESH : Fibroblasts, Humans, MESH : Astronauts, Radiology, Nuclear Medicine and imaging, history, Relative Biological Effectiveness, Space Flight, MESH : Relative Biological Effectiveness, MESH: Cytogenetics, 030304 developmental biology, MESH: DNA Damage, MESH: Humans, MESH : Space Flight, MESH : Humans, 21st Century, Humans, Microscopy, Radiobiology, Fibroblasts, History, 20th Century, Space Flight, Space radiation, methods, Radiation Dosage, Radiobiology, Microscopy, Fluorescence, MESH: Fibroblasts, Repeated doses, MESH : Radiobiology, Dose rate, MESH : History, 21st Century, Cosmic Radiation, Relative Biological Effectiveness, DNA Damage, MESH : History, 20th Century
Abstract

International audience; Exposure to radiation is one of the main concerns for space exploration by humans. By focusing deliberately on the works performed on human cells, we endeavored to review, decade by decade, the technological developments and conceptual advances of space radiation biology. Despite considerable efforts, the cancer and the toxicity risks remain to be quantified: 1) the nature and the frequency of secondary heavy ions need to be better characterized in order to estimate their contribution to the dose and to the final biological response; 2) the diversity of radiation history of each astronaut and the impact of individual susceptibility make very difficult any epidemiological analysis for estimating hazards specifically due to space radiation exposure. 3) Cytogenetic data undoubtedly revealed that space radiation exposure produce significant damage in cells. However, our knowledge of the basic mechanisms specific to low-dose, to repeated doses and to adaptive response is still poor. The application of new radiobiological techniques, like immunofluorescence, and the use of human tissue models different from blood, like skin fibroblasts, may help in clarifying all the above items.

Published
2011

5. A novel mutation of the ACADM gene (c.145C>G) associated with the common c.985A>G mutation on the other ACADM allele causes mild MCAD deficiency: a case report

Author

Daniel Rabier, Silvia Napuri-Gouel, Annie Martin-Ponthieu, Michèle Brivet, Niels Gregersen, Monique Fontaine, Brage S. Andresen, Gilbert Briand, Karine Mention-Mulliez, Dries Dobbelaere, Christine Vianey-Saban, Ronald J.A. Wanders, Joseph Vamecq, Anne-Frédérique Dessein, David S. Millington, Laboratoire d'hormonologie, métabolisme-nutrition et oncologie (HMNO), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Research Unit for Molecular Medicine, Aarhus University [Aarhus]-Institute of Clinical Medicine, Department of Biochemistry and Molecular Biology, University of Southern Denmark (SDU), Service de biochimie métabolique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Biochimie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de neurologie pédiatrique, branche épilepsie, Centre de référence des maladies métaboliques héréditaires, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire d'application de Spectrométrie de Masse (LASM), Université de Lille, Droit et Santé, Department of Paediatrics, Duke University Medical Center, Centre de biologie et pathologie Est, Hospices Civils de Lyon (HCL), Laboratory of Genetic Metabolic Diseases, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), This work was supported by grants from the French Ministère de la Santé (PHRC 2003R/ 1903) and FMO (Fédération des Maladies Orphelines)., Aarhus University [Aarhus] - Institute of Clinical Medicine, UNIVERSITY OF SOUTHERN DENMARK, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bicêtre, Hôpital Jeanne de Flandre [Lille] - Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Academic Medical Center [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA) - University of Amsterdam [Amsterdam] (UvA), Faculteit der Geneeskunde, BMC, Ed., Amsterdam Gastroenterology Endocrinology Metabolism, and Laboratory Genetic Metabolic Diseases

Subjects
Male, MESH: Oxidation-Reduction, MESH : Lymphocytes, lcsh:Medicine, MESH : Carnitine, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH : Child, Preschool, Compound heterozygosity, Polymerase Chain Reaction, Acyl-CoA Dehydrogenase, 0302 clinical medicine, Genetics(clinical), MESH : Female, Pharmacology (medical), Lymphocytes, MESH : Acyl-CoA Dehydrogenase, MESH : Polymerase Chain Reaction, MESH : Fatty Acids, Cells, Cultured, Genetics (clinical), Skin, Medicine(all), Genetics, 0303 health sciences, MESH: Carnitine, Fatty Acids, MESH: Genetic Predisposition to Disease, MESH: Acyl-CoA Dehydrogenase, General Medicine, MESH : Adult, Pedigree, MESH: Fatty Acids, 3. Good health, Child, Preschool, Mutation (genetic algorithm), Female, MESH : Mutation, Oxidation-Reduction, ACADM Gene, MESH: Cells, Cultured, medicine.drug, Adult, medicine.medical_specialty, MESH: Mutation, MESH: Pedigree, MESH : Male, Biology, 03 medical and health sciences, MESH : Deficiency Diseases, MESH: Skin, Carnitine, Internal medicine, MESH : Cells, Cultured, MESH : Fibroblasts, MESH : Skin, medicine, Humans, Genetic Predisposition to Disease, ACADM, 030304 developmental biology, MESH : Oxidation-Reduction, [SDV.GEN]Life Sciences [q-bio]/Genetics, Newborn screening, MESH: Humans, Research, lcsh:R, MESH : Humans, MESH: Child, Preschool, Acyl CoA dehydrogenase, MESH: Adult, MESH: Polymerase Chain Reaction, Fibroblasts, MCADD, medicine.disease, MESH: Male, Endocrinology, MESH: Deficiency Diseases, MESH: Fibroblasts, MESH : Pedigree, Mutation, biology.protein, MESH : Genetic Predisposition to Disease, MESH: Lymphocytes, Deficiency Diseases, MESH: Female, 030217 neurology & neurosurgery
Abstract

A female patient, with normal familial history, developed at the age of 30 months an episode of diarrhoea, vomiting and lethargy which resolved spontaneously. At the age of 3 years, the patient re-iterated vomiting, was sub-febrile and hypoglycemic, fell into coma, developed seizures and sequels involving right hemi-body. Urinary excretion of hexanoylglycine and suberylglycine was low during this metabolic decompensation. A study of pre- and post-prandial blood glucose and ketones over a period of 24 hours showed a normal glycaemic cycle but a failure to form ketones after 12 hours fasting, suggesting a mitochondrial β-oxidation defect. Total blood carnitine was lowered with unesterified carnitine being half of the lowest control value. A diagnosis of mild MCAD deficiency (MCADD) was based on rates of 1-14C-octanoate and 9, 10-3H-myristate oxidation and of octanoyl-CoA dehydrogenase being reduced to 25% of control values. Other mitochondrial fatty acid oxidation proteins were functionally normal. De novo acylcarnitine synthesis in whole blood samples incubated with deuterated palmitate was also typical of MCADD. Genetic studies showed that the patient was compound heterozygous with a sequence variation in both of the two ACADM alleles; one had the common c.985A>G mutation and the other had a novel c.145C>G mutation. This is the first report for the ACADM gene c.145C>G mutation: it is located in exon 3 and causes a replacement of glutamine to glutamate at position 24 of the mature protein (Q24E). Associated with heterozygosity for c.985A>G mutation, this mutation is responsible for a mild MCADD phenotype along with a clinical story corroborating the emerging literature view that patients with genotypes representing mild MCADD (high residual enzyme activity and low urinary levels of glycine conjugates), similar to some of the mild MCADDs detected by MS/MS newborn screening, may be at risk for disease presentation.

Published
2010
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6. Lysosomal serine protease CLN2 regulates tumor necrosis factor-alpha-mediated apoptosis in a Bid-dependent manner

Author

Nathalie Andrieu-Abadie, Virginie Garcia, Hélène Autefage, Nicole Therville, Thierry Levade, Marie-Françoise Altié, Catherine Caillaud, Virginie Albinet, Hortense Berges, Marie-Laure Nicolau, Institut de médecine moléculaire de Rangueil ( I2MR ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and Simon, Marie Francoise

Subjects
Small interfering RNA, MESH : Cytochromes c, MESH: Neurons, MESH: Cricetinae, Apoptosis, MESH: Caspase 9, Biochemistry, Aminopeptidases, MESH: Recombinant Proteins, MESH: Cricetulus, Cricetinae, MESH: Caspase 3, MESH : CHO Cells, MESH : Catalysis, MESH: Animals, MESH : Caspase 3, MESH: Endopeptidases, Caspase, Neurons, MESH : Tumor Necrosis Factor-alpha, biology, Tripeptidyl-Peptidase 1, MESH : Caspase 9, Caspase 3, Mechanisms of Signal Transduction, MESH : Cricetinae, Cytochromes c, Transfection, MESH: Cytochromes c, Caspase 9, Recombinant Proteins, MESH : Endopeptidases, Cell biology, Tumor necrosis factor alpha, BH3 Interacting Domain Death Agonist Protein, Programmed cell death, Proteases, MESH : Recombinant Proteins, MESH : Cricetulus, MESH: BH3 Interacting Domain Death Agonist Protein, CHO Cells, Catalysis, MESH : Neurons, Cricetulus, MESH: CHO Cells, Endopeptidases, MESH : Fibroblasts, Animals, Humans, MESH : BH3 Interacting Domain Death Agonist Protein, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Molecular Biology, Serine protease, MESH: Humans, Tumor Necrosis Factor-alpha, MESH: Apoptosis, MESH : Humans, Cell Biology, Fibroblasts, MESH : Lysosomes, MESH: Catalysis, Molecular biology, MESH: Fibroblasts, MESH: Tumor Necrosis Factor-alpha, biology.protein, MESH : Animals, Serine Proteases, Lysosomes, MESH : Apoptosis, MESH: Lysosomes
Abstract

International audience; Apoptosis is a highly organized, energy-dependent program by which multicellular organisms eliminate damaged, superfluous, and potentially harmful cells. Although caspases are the most prominent group of proteases involved in the apoptotic process, the role of lysosomes has only recently been unmasked. This study investigated the role of the lysosomal serine protease CLN2 in apoptosis. We report that cells isolated from patients affected with late infantile neuronal ceroid lipofuscinosis (LINCL) having a deficient activity of CLN2 are resistant to the toxic effect of death ligands such as tumor necrosis factor (TNF), CD95 ligand, or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but not to receptor-independent stress agents. CLN2-deficient cells exhibited a defect in TNF-induced Bid cleavage, release of cytochrome c, and caspase-9 and -3 activation. Moreover, extracts from CLN2-overexpressing cells or a CLN2 recombinant protein were able to catalyze the in vitro cleavage of Bid. Noteworthy, correction of the lysosomal enzyme defect of LINCL fibroblasts using a medium enriched in CLN2 protein enabled restoration of TNF-induced Bid and caspase-3 processing and toxicity. Conversely, transfection of CLN2-corrected cells with small interfering RNA targeting Bid abrogated TNF-induced cell death. Altogether, our study demonstrates that genetic deletion of the lysosomal serine protease CLN2 and the subsequent loss of its catalytic function confer resistance to TNF in non-neuronal somatic cells, indicating that CLN2 plays a yet unsuspected role in TNF-induced cell death.

Published
2009
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7. [How I perform... the closure of laparoscopic port sites with the Reverdin needle]

Author

J-J, Terzibachian, B, Chung Fat, R, Ramanah, F, Leung, A, Grisey, T, de Lapparent, D, Riethmuller, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), and Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC )

Subjects
MESH: Nerve Regeneration, MESH : Needles, MESH : Laparoscopy, MESH: Laparoscopy, MESH : Tissue Scaffolds, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH : Nerve Growth Factor, MESH: Collagen, MESH : Bone and Bones, MESH: Tissue Scaffolds, MESH: Animals, MESH : Laminin, MESH: Fibrin, health care economics and organizations, MESH: Nerve Growth Factor, MESH : Suture Techniques, MESH : Peripheral Nerves, MESH: Laminin, MESH : Neurosurgical Procedures, MESH: Bone and Bones, Laparoscopes, MESH : Fibrin, surgical procedures, operative, Needles, MESH : Vascular Endothelial Growth Factor A, MESH : Nerve Regeneration, cardiovascular system, MESH : Laparoscopes, MESH: Glial Cell Line-Derived Neurotrophic Factor, MESH : Glial Cell Line-Derived Neurotrophic Factor, MESH: Fibroblast Growth Factors, MESH: Neuregulin-1, MESH : Neuregulin-1, MESH : Schwann Cells, MESH: Laparoscopes, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Suture Techniques, MESH : Fibroblast Growth Factors, MESH : Fibroblasts, Humans, cardiovascular diseases, MESH: Ciliary Neurotrophic Factor, MESH: Humans, MESH: Vascular Endothelial Growth Factor A, Suture Techniques, MESH : Humans, MESH: Neurosurgical Procedures, MESH: Peripheral Nerves, MESH : Ciliary Neurotrophic Factor, MESH: Needles, MESH: Fibroblasts, MESH : Stromal Cells, MESH : Collagen, Laparoscopy, MESH : Animals, MESH: Stromal Cells, MESH: Schwann Cells
Abstract

International audience; The use of nerve conduits as an alternative for nerve grafting has a long experimental and clinical history. Luminal additives, factors introduced into these nerve conduits, were later developed to enhance the nerve regeneration through conduits. This chapter generalizes the types of additives used, and the reported performance of luminal additives in conduits to present a preference list for the most effective additives to use over specific distances of nerve defect.

Published
2009
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8. Putative functional domains of human cytomegalovirus pUL56 involved in dimerization and benzimidazole D-ribonucleoside activity

Author

Armelle Rametti, Serge Bouaziz, François Denis, Sébastien Hantz, Sophie Alain, Marie-Christine Mazeron, Anthony Couvreux, Gaël Champier, Biologie moléculaire et cellulaire des microorganismes (EA3175), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Limoges (UNILIM), Hôpital Lariboisière, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC), Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, Laboratoire de Biochimie Pharmaceutique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Laboratoire d'informatique Fondamentale de Marseille - UMR 6166 (LIF), Université de la Méditerranée - Aix-Marseille 2-Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bouaziz, Serge, Université de Rennes (UR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Limoges (UNILIM) - Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503) - Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Lariboisière - Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5) - Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), and Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP) - Centre National de la Recherche Scientifique (CNRS) - Institut de Recherche pour le Développement (IRD) - Université Paris Descartes - Paris 5 (UPD5)

Subjects
Human cytomegalovirus, Models, Molecular, MESH: Sequence Analysis, DNA, MESH : Molecular Sequence Data, viruses, Cytomegalovirus, MESH: Amino Acid Sequence, medicine.disease_cause, MESH : Ribonucleosides, chemistry.chemical_compound, Letermovir, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pharmacology (medical), MESH : DNA, Viral, Cells, Cultured, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], MESH : Amino Acid Sequence, MESH : Viral Structural Proteins, virus diseases, Infectious Diseases, MESH : Benzimidazoles, Biochemistry, MESH : Dimerization, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Dna packaging, Dimerization, MESH: Models, Molecular, MESH : Virus Assembly, medicine.drug, MESH: Cells, Cultured, Benzimidazole, MESH: Cytomegalovirus, MESH: Virus Assembly, MESH : Models, Molecular, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Molecular Sequence Data, MESH: Viral Structural Proteins, Virus, Herpesviridae, MESH : Cytomegalovirus, Betaherpesvirinae, MESH : Cells, Cultured, MESH : Fibroblasts, medicine, Humans, Amino Acid Sequence, Pharmacology, Viral Structural Proteins, MESH: Ribonucleosides, MESH: Humans, MESH: Molecular Sequence Data, Virus Assembly, MESH : Humans, Sequence Analysis, DNA, Fibroblasts, biochemical phenomena, metabolism, and nutrition, Ribonucleoside, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: DNA, Viral, chemistry, MESH: Dimerization, MESH: Fibroblasts, DNA, Viral, Benzimidazoles, Ribonucleosides, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Benzimidazoles, MESH : Sequence Analysis, DNA
Abstract

Background Benzimidazole d-ribonucleosides inhibit DNA packaging during human cytomegalovirus (HCMV) replication. Although they have been shown to target pUL56 and pUL89 (the large and small subunits of the HCMV terminase, respectively) their mechanism of action is not yet fully understood. We aimed here to better understand HCMV DNA maturation and the mechanism of action of benzimidazole derivatives. Methods The HCMV pUL56 protein was studied by sequence analysis of the HCMV UL56 gene and herpesvirus counterparts combined with primary structure analysis of the corresponding amino acid sequences. Results The UL56 sequence analysis of 45 HCMV strains and counterparts among herpesviruses allowed the identification of 12 conserved regions. Moreover, comparison with the product of gene 49 (gp49) of bacteriophage T4 suggested that the pUL56 zinc finger is localized close to the dimerization site of pUL56, providing a spatial organization of the catalytic site that allows recognition and cleavage of DNA. Conclusions This study provides a basis to investigate the mechanism of concatemeric DNA cleavage and a biochemical basis for DNA packaging inhibition by benzimidazole derivatives.

Published
2008

9. Human bone marrow-derived cells: an attractive source to populate dermal substitutes

Author

Philippe Humbert, Myriam Yousfi, Florence Fioretti, Alexis Desmoulière, Corinne Lebreton-Decoster, Gaston Godeau, Farida Gueniche, Bernard Coulomb, Karim Senni, Réparation et remodelage oro-fasciaux, Université Paris Descartes - Paris 5 (UPD5), Interactions de l'épithelium intestinal avec le système immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université de Limoges (UNILIM), Homéostasie Cellulaire et Pathologies (HCP), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Réparation artérielle (EA 4060), Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Université de Limoges ( UNILIM ), Homéostasie Cellulaire et Pathologies ( HCP ), Université de Limoges ( UNILIM ) -CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ), Réparation artérielle ( EA 4060 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Saas, Philippe, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)

Subjects
MESH : Wound Healing, Vimentin, Matrix metalloproteinase, Matrix (biology), 030207 dermatology & venereal diseases, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH: Animals, Cells, Cultured, 0303 health sciences, MESH: Middle Aged, biology, integumentary system, Chemistry, MESH : Rats, MESH: Bone Marrow Cells, Anatomy, Dermis, Middle Aged, MESH : Adult, Cell biology, MESH : Skin, Artificial, medicine.anatomical_structure, MESH: Skin, Artificial, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH: Cells, Cultured, Adult, Cell type, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Rats, Bone Marrow Cells, Dermatology, MESH : Rats, Wistar, Dermal fibroblast, 03 medical and health sciences, MESH : Cells, Cultured, MESH : Fibroblasts, medicine, Animals, Humans, MESH : Middle Aged, Rats, Wistar, 030304 developmental biology, Skin, Artificial, Wound Healing, MESH: Humans, MESH : Humans, MESH : Dermis, MESH: Adult, MESH: Rats, Wistar, Fibroblasts, MESH: Dermis, Rats, MESH: Wound Healing, MESH: Fibroblasts, biology.protein, Surgery, Desmin, MESH : Animals, Wound healing, MESH: Female, MESH : Bone Marrow Cells
Abstract

ACL-92; MMNP; International audience; We have previously shown the importance of dermal fibroblasts within skin substitutes for promoting the emergence of a functional neodermis after grafting in humans. However, the use of fibroblasts from sources other than the dermis needs to be evaluated for patients with extensive skin loss. Here we examined the capacity of human bone marrow-derived cells (BMDCs), selected for their ability to adhere to plastic culture dishes, to behave like human dermal fibroblasts when incorporated within a 3D in vitro reconstructed tissue that promotes dermal fibroblast differentiation. Like dermal fibroblasts, BMDCs contracted a collagen matrix and were growth regulated by the matrix environment. They had the same shape and their nuclei had the same form factor as dermal fibroblasts. In addition, both cell types expressed desmin and vimentin but not alpha-smooth muscle actin. BMDCs deposited collagen types I and III, and fibrillin-1 with similar efficiency to dermal fibroblasts. In addition, BMDCs have the potential to regulate this deposition, as they produced metalloproteinases (MMP1, MMP2, and MMP9) and metalloproteinase inhibitors (TIMP1) very similarly to dermal fibroblasts. BMDCs can thus be induced to express functions resembling those of dermal fibroblasts, including those involved in the wound healing process.

Published
2008
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10. TLR3 deficiency in patients with herpes simplex encephalitis

Author

Vanessa Sancho-Shimizu, Armanda Casrouge, Pedro Romero, Flore Rozenberg, Capucine Picard, Anne Puel, Lluis Quintana-Murci, Asma Smahi, Bénédicte Héron, Frederic Geissmann, Lazaro Lorenzo, Joshua N. Leonard, Jean-Laurent Casanova, Matthias Titeux, Louis Vallée, Luis B. Barreiro, Eric Vivier, Céline Cognet, Horst von Bernuth, Alain Hovnanian, Gaelle Elain, Marc Tardieu, David J. Segal, Shen-Ying Zhang, Emmanuelle Jouanguy, Claire Hamilton, Cheng-Lung Ku, Pierre Lebon, Ariane Chapgier, Laurent Abel, Sophie Ugolini, Sabine Plancoulaine, Xin Xin Zhang, Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), and Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )

Subjects
Keratinocytes, MESH : Cell Line, viruses, MESH : Toll-Like Receptor 3, MESH : Immunity, Natural, Herpesvirus 1, Human, CD8-Positive T-Lymphocytes, MESH : Child, Preschool, medicine.disease_cause, 0302 clinical medicine, MESH : Interferons, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Interferons, MESH : Female, Genes, Dominant, MESH: Heterozygote, 0303 health sciences, Toll-like receptor, Multidisciplinary, MESH: Dendritic Cells, MESH : Keratinocytes, MESH: Encephalitis, Herpes Simplex, virus diseases, hemic and immune systems, MESH : Infant, MESH : Genes, Dominant, MESH: Toll-Like Receptor 3, MESH : CD8-Positive T-Lymphocytes, MESH: CD8-Positive T-Lymphocytes, MESH: Infant, MESH: Keratinocytes, 3. Good health, Killer Cells, Natural, MESH: Leukocytes, Mononuclear, MESH: Herpesvirus 1, Human, Child, Preschool, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Killer Cells, Natural, MESH : Mutation, Encephalitis, MESH : Poly I-C, MESH: Killer Cells, Natural, UNC93B1, Heterozygote, MESH : Heterozygote, MESH: Mutation, chemical and pharmacologic phenomena, Biology, MESH: Poly I-C, Virus, Herpesviridae, Cell Line, 03 medical and health sciences, Immunity, MESH : Fibroblasts, medicine, Humans, Alleles, 030304 developmental biology, MESH: Immunity, Natural, Innate immune system, MESH: Humans, MESH: Alleles, MESH: Child, Preschool, MESH : Humans, Infant, Dendritic Cells, Fibroblasts, medicine.disease, Virology, MESH : Herpesvirus 1, Human, Immunity, Innate, MESH : Encephalitis, Herpes Simplex, Toll-Like Receptor 3, MESH: Cell Line, MESH : Leukocytes, Mononuclear, Herpes simplex virus, Poly I-C, MESH: Fibroblasts, MESH : Dendritic Cells, Immunology, Mutation, Leukocytes, Mononuclear, Encephalitis, Herpes Simplex, Interferons, MESH: Genes, Dominant, MESH : Alleles, MESH: Female, 030215 immunology
Abstract

International audience; Some Toll and Toll-like receptors (TLRs) provide immunity to experimental infections in animal models, but their contribution to host defense in natural ecosystems is unknown. We report a dominant-negative TLR3 allele in otherwise healthy children with herpes simplex virus 1 (HSV-1) encephalitis. TLR3 is expressed in the central nervous system (CNS), where it is required to control HSV-1, which spreads from the epithelium to the CNS via cranial nerves. TLR3 is also expressed in epithelial and dendritic cells, which apparently use TLR3-independent pathways to prevent further dissemination of HSV-1 and to provide resistance to other pathogens in TLR3-deficient patients. Human TLR3 appears to be redundant in host defense to most microbes but is vital for natural immunity to HSV-1 in the CNS, which suggests that neurotropic viruses have contributed to the evolutionary maintenance of TLR3.

Published
2007
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11. Skin involvement in scleroderma--where histological and clinical scores meet

Author

Raphaël Porcher, Laurence Michel, Patrick Bruneval, Franck Verrecchia, Kiet Phuong Tiev, M. Ertault, O. Verola, Dominique Farge, Alain Mauviel, Nina Roos, J. Laboureau, Bases Moleculaires de l'Homeostasie Cutanee : Inflammation, Reparation et Cancer, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Biostatistique et épidemiologie clinique, Service d'anatomo-pathologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Service greffe de moelle osseuse, Service de médecine interne, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Service de Médecine Interne [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de médecine interne [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de médecine interne [CHU Saint-Antoine], and Verrecchia, Franck

Subjects
Male, Pathology, Systemic disease, MESH: Combined Modality Therapy, MESH : Peripheral Blood Stem Cell Transplantation, Biopsy, MESH : Aged, Smad Proteins, MESH: Peripheral Blood Stem Cell Transplantation, Systemic scleroderma, Severity of Illness Index, Scleroderma, Immunoenzyme Techniques, MESH: Biopsy, 0302 clinical medicine, Fibrosis, Transforming Growth Factor beta, Immunopathology, MESH: Collagen, Pharmacology (medical), MESH: Double-Blind Method, MESH : Female, Phosphorylation, MESH : Immunosuppressive Agents, Cells, Cultured, Skin, MESH: Aged, 0303 health sciences, MESH: Phosph, MESH: Middle Aged, medicine.diagnostic_test, integumentary system, Middle Aged, MESH : Adult, Connective tissue disease, Combined Modality Therapy, 3. Good health, MESH: Fibrosis, MESH : Fibrosis, Female, Collagen, MESH: Immunosuppressive Agents, Reticular Dermis, Immunosuppressive Agents, Signal Transduction, MESH: Cells, Cultured, Adult, medicine.medical_specialty, MESH : Male, Collagen Type I, 03 medical and health sciences, Rheumatology, Double-Blind Method, MESH : Immunoenzyme Techniques, Plasminogen Activator Inhibitor 1, MESH : Cells, Cultured, MESH : Fibroblasts, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, MESH : Double-Blind Method, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Middle Aged, RNA, Messenger, Smad3 Protein, MESH: Immunoenzyme Techniques, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Aged, 030203 arthritis & rheumatology, Peripheral Blood Stem Cell Transplantation, MESH: Humans, business.industry, MESH : Phosph, MESH : Humans, MESH: Adult, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, Fibroblasts, medicine.disease, MESH: Male, MESH: Fibroblasts, MESH : Biopsy, Scleroderma, Diffuse, MESH : Collagen, business, MESH : Combined Modality Therapy, [ SDV.MHEP.DERM ] Life Sciences [q-bio]/Human health and pathology/Dermatology, MESH: Female, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract

International audience; OBJECTIVES: A clinico-pathological study in diffuse systemic sclerosis (SSc) patients was performed to analyse whether the skin histological organization and the pro-fibrotic signals elicited by TGF-beta in fibroblasts vary according to the modified Rodnan skin score (mRSS). METHODS: Twenty-seven SSc patients underwent 45 skin biopsies with simultaneous measure of mRSS before or after treatment by immunosuppressive drugs, with or without autologous peripheral haematopoietic stem cell transplantation (HSCT). RESULTS: Double-blind optic microscopy analysis of the biopsies standard extracellular matrix stains allowed to define three histological subgroups: 6 with grade 1 weak fibrosis, 30 with grade 2 moderate fibrosis and 9 with grade 3 severe fibrosis. A significant (P < 0.0001) was identified between the grades of fibrosis and the mRSS. In skin fibroblast cultures, Smad3 phosphorylation levels, as well as mRNA steady-state levels of two transforming growth factor (TGF)-beta/Smad3 targets, COL1A2 and PAI-1, increased in parallel with the mRSS. When compared with pre-transplant values the degree of fibrosis observed after HSCT in the papillary and in the reticular dermis decreased in parallel with the fall in mRSS (n = 5 consecutive patients with repeated biopsies). CONCLUSIONS: The histological extent of skin fibrosis correlates closely with the mRSS. Both parameters appeared to regress after HSCT. The extent of TGF-beta signalling activation in SSc skin fibroblasts appears to parallel the severity of disease.

Published
2007
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12. Comparison of ultraviolet B-induced imbalance of antioxidant status in foreskin- and abdominal skin-derived human fibroblasts

Author

Saguet, Thibaut, Robin, Sophie, Nicod, Laurence, Delphine Binda, Viennet, Céline, Aubin, François, Coulomb, Bernard, Humbert, Philippe, Laboratoire d'Ingénierie et Biologie Cutanées ( LIBC ), IFR33-Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Université de Franche-Comté ( UFC ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), BioExigence, BioExigence SARL, Sciences séparatives et biopharmaceutiques, Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Université de Franche-Comté ( UFC ), Réparation et remodelage oro-fasciaux, Université Paris Descartes - Paris 5 ( UPD5 ), Département de dermatologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques-Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Laboratoire d'Ingénierie et Biologie Cutanées (LIBC), IFR33-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université de Franche-Comté (UFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and Saas, Philippe

Subjects
MESH: Oxidation-Reduction, Adult, Male, [SDV.IMM] Life Sciences [q-bio]/Immunology, Ultraviolet Rays, MESH : Male, Foreskin, MESH : Abdomen, MESH : Foreskin, MESH : Child, Preschool, MESH: Abdomen, MESH: Skin, MESH : Child, MESH: Child, MESH : Cells, Cultured, MESH : Fibroblasts, Abdomen, MESH : Skin, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, Child, MESH: Foreskin, Cells, Cultured, Skin, MESH : Oxidation-Reduction, MESH: Humans, integumentary system, MESH: Child, Preschool, MESH : Humans, MESH: Adult, MESH : Adult, Fibroblasts, MESH: Male, MESH: Fibroblasts, MESH : Ultraviolet Rays, Child, Preschool, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Ultraviolet Rays, Oxidation-Reduction, MESH: Cells, Cultured
Abstract

International audience; Ultraviolet B radiation (UVB) is involved in the development of deleterious cutaneous damage. Several changes could be attributed to UVB-induced reactive oxygen species attacks in fibroblasts. However dermal cells from young and adult skin could respond differently to oxidative stress. So antioxidant status and its consequences on cytotoxicity and apoptosis were compared in child foreskin fibroblasts (FF) and adult abdominal skin fibroblasts (AF) in response to UVB. Basal levels of lipid peroxidation tended to be higher in AF than in FF, which could be related to a reshaping of antioxidant defences (higher catalase and lower superoxide dismutase activities). AF and FF appeared to react similarly to high UVB doses as regards cytotoxicity and apoptosis which increased significantly 24h after exposure. The enhancement of cell death could be due to the inherent oxidative stress: glutathione appeared significantly decreased in both cell populations. As a consequence AF, but not FF, presented significantly increased levels of lipid peroxidation, which could be explained by the pre-cited differences of basal antioxidant defences. These results suggest that AF and FF do not respond to UVB by the same pathway.

Published
2006

13. Mitochondrial activities in human cultured skin fibroblasts contaminated by Mycoplasma hyorhinis

Author

Darin, Niklas, Kadhom, Norman, Brière, Jean-Jacques, Chretien, Dominique, Bébéar, Cécile M, Rötig, Agnès, Munnich, Arnold, Rustin, Pierre, Handicaps génétiques de l'enfant (Inserm U393), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Bactériologie, Université Bordeaux Segalen - Bordeaux 2, This project was supported by Grants from the Wenner-Gren Foundations, the Swedish Association of Neurologically Disabled, the Swedish Medical Association and the Association Française contre l'Ataxie de Friedreich (AFAF), Maylin, Françoise, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Handicaps génétiques de l'enfant ( Inserm U393 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
Mycoplasma hyorhinis, Cell Culture Techniques, MESH : Aged, lcsh:Animal biochemistry, MESH : Child, Preschool, MESH: Research Support, Non-U.S. Gov't, Phosphate Acetyltransferase, MESH : Research Support, Non-U.S. Gov't, MESH : Child, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Child, lcsh:QD415-436, Child, Cells, Cultured, Skin, MESH: Aged, MESH: Middle Aged, Middle Aged, MESH : Adult, Mitochondria, MESH : Phosphate Acetyltransferase, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Child, Preschool, MESH: Mycoplasma hyorhinis, MESH : Mitochondria, Research Article, MESH: Cells, Cultured, Adult, MESH : Cell Culture Techniques, Adolescent, MESH: Mitochondria, Cell Respiration, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, lcsh:Biochemistry, MESH: Skin, MESH : Adolescent, MESH : Cells, Cultured, MESH : Fibroblasts, MESH : Skin, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, MESH : Middle Aged, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Phosphate Acetyltransferase, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, lcsh:QP501-801, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Aged, MESH: Adolescent, MESH: Cell Culture Techniques, MESH: Humans, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH : Humans, MESH: Child, Preschool, MESH: Adult, Fibroblasts, MESH: Fibroblasts, MESH : Cell Respiration, MESH : Mycoplasma hyorhinis, MESH: Cell Respiration
Abstract

Background Mycoplasma contaminations are a recurrent problem in the use of cultured cells, including human cells, especially as it has been shown to impede cell cycle, triggering cell death under various conditions. More specific consequences on cell metabolism are poorly known. Results Here we report the lack of significant consequence of a heavy contamination by the frequently encountered mycoplasma strain, M. hyorhinis, on the determination of respiratory chain activities, but the potential interference when assaying citrate synthase. Contamination by M. hyorhinis was detected by fluorescent imaging and further quantified by the determination of the mycoplasma-specific phosphate acetyltransferase activity. Noticeably, this latter activity was not found equally distributed in various mycoplasma types, being exceptionally high in M. hyorhinis. Conclusion While we observed a trend for respiration reduction in heavily contaminated cells, no significant and specific targeting of any respiratory chain components could be identified. This suggested a potential interference with cell metabolism rather than direct interaction with respiratory chain components.

Published
2003
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14. Interleukin-1beta induces glycosaminoglycan synthesis via the prostaglandin E2 pathway in cultured human cervical fibroblasts

Author

Michelle Breuiller-Fouché, Françoise Ferré, Thomas Schmitz, Dominique Cabrol, Emmanuelle Dallot, Marie-Josèphe Leroy, Breuiller-Fouche, Michelle, La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus (UMR_S 767), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maternité Port-Royal [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomique et épigénétique des pathologies placentaires (Inserm U709), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), La grossesse normale et pathologique: développement et fonctions du placenta et de l'utérus ( UMR_S 767 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Génomique et épigénétique des pathologies placentaires ( Inserm U709 ), and Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 )

Subjects
MESH : RNA, Messenger, Transcription, Genetic, medicine.medical_treatment, MESH: Sulfonamides, Cervix Uteri, MESH: Base Sequence, 0302 clinical medicine, Cells, Cultured, Glycosaminoglycans, MESH : Isoenzymes, Sulfonamides, 0303 health sciences, 030219 obstetrics & reproductive medicine, MESH: Dinoprostone, MESH: Cervix Uteri, Receptors, Prostaglandin E, EP3 Subtype, MESH : Biphenyl Compounds, MESH : DNA Primers, MESH: Membrane Proteins, Prostaglandin E, MESH: Cells, Cultured, MESH: DNA Primers, medicine.medical_specialty, MESH : Cyclooxygenase 2, MESH: Prostaglandin-Endoperoxide Synthases, Dinoprostone, Article, 03 medical and health sciences, MESH: Cyclooxygenase Inhibitors, MESH : Fibroblasts, Genetics, Humans, Cyclooxygenase Inhibitors, RNA, Messenger, Molecular Biology, Nitrobenzenes, MESH: Humans, Cyclooxygenase 2 Inhibitors, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Biphenyl Compounds, MESH : Humans, MESH: Interleukin-1, Fibroblasts, Receptors, Prostaglandin E, EP2 Subtype, MESH : Nitrobenzenes, Endocrinology, Reproductive Medicine, MESH : Membrane Proteins, MESH: Female, Developmental Biology, Embryology, MESH: Cyclooxygenase 2 Inhibitors, MESH: Receptors, Prostaglandin E, MESH : Cyclooxygenase 2 Inhibitors, MESH : Female, Prostaglandin E2, Receptor, MESH : Prostaglandin-Endoperoxide Synthases, MESH: Kinetics, Obstetrics and Gynecology, Interleukin, MESH: Glycosaminoglycans, MESH : Cyclooxygenase Inhibitors, Receptor antagonist, Receptors, Prostaglandin E, EP1 Subtype, Isoenzymes, MESH: Isoenzymes, lipids (amino acids, peptides, and proteins), Female, Signal transduction, MESH : Kinetics, MESH: Cyclooxygenase 2, MESH : Receptors, Prostaglandin E, MESH: Biphenyl Compounds, medicine.drug, MESH : Dinoprostone, medicine.drug_class, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH : Interleukin-1, Paracrine signalling, Internal medicine, MESH : Cells, Cultured, medicine, MESH : Glycosaminoglycans, Receptors, Prostaglandin E, Autocrine signalling, MESH : Sulfonamides, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, DNA Primers, 030304 developmental biology, MESH: RNA, Messenger, Base Sequence, MESH: Transcription, Genetic, Membrane Proteins, MESH : Transcription, Genetic, MESH: Nitrobenzenes, Cell Biology, Kinetics, Cyclooxygenase 2, Prostaglandin-Endoperoxide Synthases, MESH: Fibroblasts, MESH : Cervix Uteri, MESH : Base Sequence, Receptors, Prostaglandin E, EP4 Subtype, Interleukin-1
Abstract

International audience; The aim of this study was to identify, in cultured human cervical fibroblasts, the mechanisms by which interleukin (IL)-1beta induces the synthesis of glycosaminoglycans (GAG) and to explore the putative role of prostaglandin E(2) (PGE(2)) in this process. Exposure of the cells for 24 h to IL-1beta induced a significant (P < 0.05) dose-dependent increase in GAG synthesis. IL-1beta (1 ng/ml) induced the expression of cyclooxygenase-2 (COX-2) protein 6 h after treatment, accompanied by a 7.5-fold increase in PGE(2) production. We confirmed that NS398, a selective COX-2 inhibitor, dose-dependently blocked PGE(2) augmentation following IL-1beta treatment. AH23848, the selective EP(4) receptor antagonist, completely abolished IL-1beta-induced GAG synthesis, whereas AH6809, an EP(2) receptor antagonist, had no effect on the stimulatory effects of IL-1beta. Furthermore, we demonstrated that 6 h exposure to IL-1beta induced a notable increase in EP(4) receptor mRNA expression and a decrease in EP(1) receptor mRNA but had no effect on the expression of EP(2) and EP(3) receptor transcripts. In conclusion, these findings indicate that IL-1beta not only induced GAG synthesis by increasing COX-2 protein expression and the subsequent PGE(2) production but also enhanced the responsiveness of cervical fibroblasts to PGE(2) by selectively up-regulating EP(4) receptor mRNA expression. These results suggest that PGE(2) may regulate human cervical ripening in an autocrine/paracrine manner via EP(4) receptors.

Published
2003

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