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1. Prevalence, Molecular Identification, and Risk Factors for Cryptosporidium Infection in Edible Marine Fish: A Survey Across Sea Areas Surrounding France

Author

Gabriela Certad, Jérôme Follet, Nausicaa Gantois, Ourida Hammouma-Ghelboun, Karine Guyot, Sadia Benamrouz-Vanneste, Emilie Fréalle, Yuwalee Seesao, Baptiste Delaire, Colette Creusy, Gaël Even, Véronique Verrez-Bagnis, Una Ryan, Mélanie Gay, Cécile Aliouat-Denis, Eric Viscogliosi, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Yncréa Hauts-de-France, Université catholique de Lille (UCL), Bio-Micro-Electro-Mechanical Systems - IEMN (BIOMEMS - IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), Institut Supérieur d'Agriculture de Lille (ISA), Université Catholique de Lille - Faculté de gestion, économie et sciences (FGES), Institut Catholique de Lille (ICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Gènes Diffusion [Douai], Plateforme d'expertises génomiques appliquées aux sciences expérimentales [Lille] (PEGASE-Biosciences), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Ecosystèmes microbiens et Molécules Marines pour les Biotechnologies (EM3B), Biotechnologies et Ressources Marines (BRM), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Centre for Sustainable Aquatic Ecosystems [Perth, WA, Australia], Murdoch University-College of Science, Health, Engineering and Education [Perth, WA, Australia], Laboratoire de sécurité des aliments de Maisons-Alfort (LSAl), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), This work was supported by the French National Research Agency (Grant No. ANR 2010 ALIA 004-01), the Conseil Regional Hauts-de-France (Concerted Research Actions of Regional Initiative, ARCir 13 ABC FISH No. 13003283), and the regional competitiveness center, AQUIMER (Boulogne s/mer, France). We wish to thank the Ifremer scientific campaigns (PELGAS. , PELMED, EVOHE, and IBTS), We dedicate this article to the memory of Eduardo Dei-Cas Dr. Slapeta for kindly providing us with the DNA from C. molnari-like genotype, and the Fish-Parasites Network., Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, YNCREA Hauts France, Partenaires INRAE, Institut Supérieur d'Agriculture [Université catholique, Lille] (ISA), Faculté de gestion, économie et sciences [UCL, Lille] (FGES), Institut Français de Recherche pour l'Exploitation de la Mer - Atlantique (IFREMER Atlantique), This work was supported by the French National Research Agency (Grant No. ANR 2010 ALIA 004-01), the Conseil Regional Hauts-de-France (Concerted Research Actions of Regional Initiative, ARCir 13 ABC FISH No. 13003283), and the regional competitiveness center, AQUIMER (Boulogne s/mer, France)., We dedicate this article to the memory of Eduardo Dei-Cas. We wish to thank the Ifremer scientific campaigns (PELGAS, PELMED, EVOHE, and IBTS), Dr. Slapeta for kindly providing us with the DNA from C. molnari-like genotype, and the Fish-Parasites Network., and Viscogliosi, Eric

Subjects
Microbiology (medical), Cryptosporidium infection, Range (biology), [SDV]Life Sciences [q-bio], lcsh:QR1-502, Zoology, Cryptosporidium, Biology, phylogeny, Microbiology, European seas, molecular epidemiology, lcsh:Microbiology, 03 medical and health sciences, Pollachius virens, parasitic diseases, medicine, 14. Life underwater, 030304 developmental biology, edible marine fish, 0303 health sciences, Molecular epidemiology, 030306 microbiology, 18S rRNA gene, Zoonosis, Aquatic animal, medicine.disease, biology.organism_classification, gp60, 3. Good health, [SDV] Life Sciences [q-bio], Cryptosporidium parvum, novel genotypes
Abstract

International audience; Cryptosporidium, a zoonotic pathogen, is able to infect a wide range of hosts including wild and domestic animals, and humans. Although it is well known that some parasites are both fish pathogens and recognized agents of zoonosis with a public health impact, little information is available concerning the prevalence of Cryptosporidium in wild aquatic environments. To evaluate the prevalence of Cryptosporidium spp. in commercially important edible marine fish in different European seas (English channel, North sea, Bay of Biscay, Celtic sea and Mediterranean sea), 1,853 specimens were collected as part of two surveys. Nested PCR followed by sequence analysis at the 18S rRNA gene locus was used to identify Cryptosporidium spp. The overall prevalence of Cryptosporidium spp. in sampled fish reached 2.3% (35 out of 1,508) in a first campaign and 3.2% (11 out of 345) in a second campaign. Sequence and phylogenetic analysis of positive samples identified Cryptosporidium parvum (n = 10) and seven genotypes which exhibited between 7.3 and 10.1% genetic distance from C. molnari, with the exception of one genotype which exhibited only 0.5-0.7% genetic distance from C. molnari. Among 31 analyzed fish species, 11 (35.5%) were identified as potential hosts for Cryptosporidium. A higher prevalence of Cryptosporidium spp. was observed in larger fish, in fish collected during the spring-summer period, and in those caught in the North East Atlantic. Pollachius virens (saithe) was the most frequently Cryptosporidium positive species. In fish infected by other parasites, the risk of being Cryptosporidium positive increased 10-fold (OR: 9.95, CI: 2.32–40.01.04, P = 0.0002). Four gp60 subtypes were detected among the C. parvum positive samples: IIaA13G1R1, IIaA15G2R1, IIaA17G2R1, and IIaA18G3R1. These C. parvum subtypes have been previously detected in terrestrial mammals and may constitute an additional source of infection for other animals and in particular for humans. Microscopical examination of histological sections confirmed the presence of round bodies suggestive of the development of C. parvum within digestive glands. We report herein the first epidemiological and molecular data concerning the detection of Cryptosporidium in edible marine fish in European seas surrounding France broadening its host range anduncovering potential novel infection routes.

Published
2019

2. Odorant binding changes the electrical properties of olfactory receptors at the nanoscale

Author

Anna Lagunas, Loïc Briand, Josep Samitier, Pau Gorostiza, Christine Belloir, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III [Madrid] (ISC)-ministerio de ciencia e innovacion, Institute for Bioengineering of Catalonia [Barcelona] (IBEC), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), Institució Catalana de Recerca i Estudis Avançats (ICREA), Universitat de Barcelona (UB), The Biomedical Research Networking Center (CIBER), Spain. CIBER is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and the Instituto de Salud Carlos III (RD16/0006/0012, RD16/0011/0022), with the support of the European Regional Development Fund (ERDF). This work was funded by the CERCA Program and by the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (2017-SGR-1079, 2017-SGR-1442 and 2017-SGR-00465). This work was supported by grants from the Conseil Régional Bourgogne Franche-Comté (PARI grant) and the FEDER (European Funding for Regional Economical Development). This research also received funding from the European Union Research and Innovation Programme Horizon 2020 (Human Brain Project SGA3 No. 945539), DEEPER (ICT-36-2020-101016787), Agency for Management of University and Research Grants of the Government of Catalonia (CERCA Programme, 2017-SGR-1442 project, AGAUR, Clúster Emergent del Cervell Humà), and Ministry of Economy and Competitiveness (Grant PID2019-111493RB-I00)., and Julien, Sabine

Subjects
Cell signaling, Olfactory receptor, Odorant binding, Chemistry, olfactory receptor, odorant binding, Impedance parameters, law.invention, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, medicine.anatomical_structure, open-circuit voltage, law, electrochemical scanning tunneling microscopy (EC-STM), impedance, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Biophysics, Scanning tunneling microscope, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Receptor, Transduction (physiology), [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Electrochemical potential
Abstract

Olfactory receptors (ORs) comprise the largest multigene family in the vertebrates. They belong to the class A (rhodopsin-like) family of G protein-coupled receptors (GPCRs), which are the most abundant membrane proteins, having widespread, significant roles in signal transduction in cells, and therefore, they are a major pharmacological target. Moreover, ORs displayed high selectivity and sensitivity towards odorant detection, a characteristic that raised the interest for developing biohybrid sensors based on ORs for the detection of volatile compounds. The transduction of odorant binding into cellular signaling by ORs is not well understood and knowing its mechanism would enable developing new pharmacology and high performance biohybrid electronic sensors. Recent findings suggest that ligand recognition by ORs is determined by the nanoscale alterations of charge distribution in the receptor structure (Ref). However, the electrical characterization of ORs and their response towards ligand binding in bulk experiments is subjected to microscopic models and assumptions [2]. Here, we have directly determined the nanoscale electrical properties of ORs with unprecedented control over the receptor orientation, and their change upon odorant binding, using electrochemical scanning tunneling microscopy (EC-STM) in near-physiological conditions. Recordings of current versus time, distance, and electrochemical potential allows determining the OR impedance parameters and their dependence with odorant binding. The simultaneous measurement of RC equivalent by means of the open-circuit voltage (VOC) allows increasing the electrical sensitivity at the single receptor level for biosensing applications. Our results allow validating OR structural-electrostatic models and their functional activation processes.

Published
2021

3. Estimating energy expenditure from accelerometer data in healthy adults and patients with type 2 diabetes

Author

Nathan Caron, Georges Dalleau, Teddy Caderby, Nicolas Peyrot, Chantal Verkindt, Ingénierie, Recherche et Intervention, Sport Santé et Environnement (IRISSE), Université de La Réunion (UR), Motricité, interaction, performance EA 4334 (MIP), Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), Université de Nantes (UN)-Université de Nantes (UN)-Le Mans Université (UM), This work was supported by a Regional Research Grant (grant #D2015033168) from the Région Réunion and from the European Regional Development Fund (FEDER), Le Mans Université (UM)-Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS), Université de Nantes (UN)-Université de Nantes (UN), Motricité, interactions, performance EA 4334 / Movement - Interactions - Performance (MIP), and Le Mans Université (UM)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR des Sciences et Techniques des Activités Physiques et Sportives (UFR STAPS)

Subjects
0301 basic medicine, Aging, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Type 2 diabetes, Biochemistry, Treadmill walking, 03 medical and health sciences, Acceleration, 0302 clinical medicine, Endocrinology, Physical medicine and rehabilitation, Diabetes mellitus, Genetics, medicine, Accelerometer data, Molecular Biology, Exercise, 2. Zero hunger, Public health, business.industry, Cell Biology, Energy metabolism, Stepwise regression, medicine.disease, 030104 developmental biology, medicine.anatomical_structure, Inertial measurement unit, Energy expenditure, Ankle, business, Body mass index, 030217 neurology & neurosurgery
Abstract

International audience; ObjectiveThe aim of this study was to develop specific prediction equations based on acceleration data measured at three body sites for estimating energy expenditure (EE) during static and active conditions in middle-aged and older adults with and without type 2 diabetes (T2D).Research methodsForty patients with T2D (age: 40–74 yr, body mass index (BMI): 21–29.4 kg·m−2) and healthy participants (age: 47–79 yr, BMI: 20.2–29.8 kg·m−2) completed trials in both static conditions and treadmill walking. For all trials, gas exchange was monitored using indirect calorimetry and vector magnitude was calculated from acceleration data measured using inertial measurement units placed to the participant's center of mass (CM), hip and ankle. Stepwise multiple regression analyses were conducted to select relevant variables to include in the three EE prediction equations, and three Monte Carlo cross-validation procedures were used to evaluate each separate equation.ResultsVector magnitude (p < 0.0001) and personal data (gender, diabetes status and BMI; p < 0.0001) were used to develop three linear prediction equations to estimate EE during static conditions and walking. Cross-validation revealed similar robust coefficients of determination (R2: 0.81 to 0.85) and small bias (mean bias: 0.008 to −0.005 kcal·min−1) for all three equations. However, the equation based on CM acceleration exhibited the lowest root mean square error (0.60 kcal·min−1 vs. 0.65 and 0.69 kcal·min−1 for the hip and ankle equations, respectively; p < 0.001).ConclusionThe three equations based on acceleration data and participant characteristics accurately estimated EE during sedentary conditions and walking in middle-aged and older adults, with or without diabetes.

Published
2020

4. Local intracerebral inhibition of IRE1 by MKC8866 sensitizes glioblastoma to irradiation/chemotherapy in vivo

Author

Qingping Zeng, Raphael Pineau, Pierre-Jean Le Reste, Afshin Samali, Amandine Etcheverry, Adrienne M. Gorman, Juhi Samal, Aristotelis Chatziioannou, Jean Mosser, Nicolas Soriano, Eric Chevet, Marc Aubry, Stéphanie Lhomond, Gwénaële Jégou, John B. Patterson, Tony Avril, Konstantinos Voutetakis, Abhay Pandit, Chemistry, Oncogenesis, Stress and Signaling (COSS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CRLCC Eugène Marquis (CRLCC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CRLCC Eugène Marquis (CRLCC), Rennes Brain Cancer Team (REACT), University of Thessaly [Volos] (UTH), National University of Ireland [Galway] (NUI Galway), Fosun Orinove PharmaTech Inc.[Newbury Park, CA], Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), CHU Pontchaillou [Rennes], National Hellenic Research Foundation [Athens], Biosit : biologie, santé, innovation technologique (SFR UMS CNRS 3480 - INSERM 018), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), This work was funded by grants from the French National Cancer Institute (INCa, PLBIO2017, 2019, 2020), the Fondation pour la recherche Médicale (FRM, équipe labellisée 2018) to EC and EU H2020 MSCA ITN-675448 (TRAINERS) and MSCA RISE-734749 (INSPIRED) grants to AS, AC and EC. The work was also supported in part by research grant from Science Foundation Ireland (SFI), co-funded under the European Regional Development Fund under Grant number 13/RC/2073., BIOSIT H2P2 platform, BIOSIT Animal facility ARCHE (https://biosit.univ-rennes1.fr/), European Project: 675448,H2020,H2020-MSCA-ITN-2015,TRAIN-ERS(2015), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
0301 basic medicine, Oncology, Cancer Research, medicine.medical_treatment, Disease, Injections, Intralesional, Mice, 0302 clinical medicine, Tumor Microenvironment, 0303 health sciences, Stress sensor, Brain Neoplasms, Combined Modality Therapy, Chemotherapy regimen, Neoadjuvant Therapy, Treatment efficacy, 3. Good health, Gene Expression Regulation, Neoplastic, Treatment Outcome, 030220 oncology & carcinogenesis, Immunocompetence, Craniotomy, medicine.medical_specialty, Morpholines, [SDV.CAN]Life Sciences [q-bio]/Cancer, IRE1, 03 medical and health sciences, Animal model, Drug Therapy, In vivo, Cell Line, Tumor, Internal medicine, medicine, Animals, Humans, Benzopyrans, 030304 developmental biology, Chemotherapy, Radiotherapy, business.industry, Gene Expression Profiling, medicine.disease, Xenograft Model Antitumor Assays, 030104 developmental biology, Unfolded protein response, Unfolded Protein Response, Tumor surgery, business, Glioblastoma, Endoplasmic reticulum
Abstract

Glioblastoma multiforme (GBM) is the most severe primary brain cancer. Despite an aggressive treatment comprising surgical resection and radio/chemotherapy patient’s survival post diagnosis remains short. A limitation for success in finding novel improved therapeutic options for such dismal disease partly lies in the lack of a relevant animal model that accurately recapitulates patient disease and standard of care. In the present study, we have developed a novel immunocompetent GBM model that includes tumor surgery and a radio/chemotherapy regimen resembling the Stupp protocol and we have used this model to test the impact of the pharmacological inhibition of the endoplasmic reticulum (ER) stress sensor IRE1, on treatment efficacy.

Published
2020

5. Impact of blade tenderization, marinade and cooking temperature on oral comfort when eating meat in an elderly population

Author

Gilles Feron, Hélène Labouré, Chantal Septier, Claire Follot, Claire Sulmont-Rossé, Mathilde Vandenberghe-Descamps, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), This study is part of AlimaSSenS [ANR-14-CE20-0003-01] funded by the French National Research Agency. This work was also supported by grants from the Regional Council of Burgundy France and the European Funding for Regional Economic Development (FEDER)., and Feron, Gilles

Subjects
0301 basic medicine, Male, Food Handling, Food bolus, Meat tenderness, Eating, Surveys and Questionnaires, Tooth loss, Roast beef, dentier, Food science, Cooking, Older adult, 2. Zero hunger, Aged, 80 and over, Temperature, food and beverages, santé bucco-dentaire, Alimentation et Nutrition, Female, medicine.symptom, Meat, Oral health, Pain, bol alimentaire, Texture perception, personne âgée, Chicken breast, 03 medical and health sciences, Tooth Loss, food, Elderly population, medicine, Food and Nutrition, Animals, Humans, Texture, Saliva, salive, Aged, Mouth, 030109 nutrition & dietetics, business.industry, food.food, Deglutition, Denture, stomatognathic diseases, older adult, food bolus, texture, oral health, denture, saliva, Mastication, Cattle, business, Chickens, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract

International audience; Several studies demonstrated that oral health impairment, such as tooth loss or a decrease in salivary flow might lead elderly people to reduce their meat intake. The present study assessed the impact of culinary processes liable to improve meat texture and smooth down meat oral processing, in order to fulfil the oral capacities of elderly people. Four culinary processes were selected: cooking bag, blade tenderizer, marinade and low-temperature cooking. A panel of 40 elderly participants with good and poor dental status were asked to assess 5 chicken breast samples, 5 roast beef samples and 4 beefsteak samples prepared according to different process conditions by using an “oral comfort” questionnaire. Results highlighted the fact that oral impairment may alter food bolus formation as well as texture perception while eating meat in elderly people. Furthermore, they revealed that easy-to-do culinary processes may improve meat tenderness and juiciness as well as smooth down food bolus formation, in particular for the roast beef.

Published
2018

6. Mouse syngenic in vitro blood–brain barrier model: a new tool to examine inflammatory events in cerebral endothelium

Author

Florence Miller, Lucie Dehouck, Yannick Delplace, Céline Morissette, Christelle Faveeuw, Caroline Coisne, Laurence Fenart, Christophe Landry, Roméo Cecchelli, Bénédicte Dehouck, Patrick Tremblay, Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Neurochem inc., This work was supported by grants from the Ministry of Research of France (fellowship to C Coisne) and by the ‘Conseil Régional du Nord-Pas-de-Calais’ (fellowship to F Miller)., and We thank Mrs Nadine Tremblay for technical assistance and Dr Valérie Buée for critical reading of the manuscript. We are very grateful to Professor B Engelhardt (Theodor Kocher Institute, University of Bern, Switzerland), Professor J Boucraut (Laboratoire NICN UMR 6184, Faculté de Médecine Timone, Marseille) and Dr MS Ghandour (Centre National de la Recherche Scientifique, Strasbourg, France) to their generous gifts of antibodies.

Subjects
Lipopolysaccharides, Endothelium, Cell Culture Techniques, Mice, Inbred Strains, P-glycoprotein, Biology, Blood–brain barrier, Cell junction, Pathology and Forensic Medicine, Mice, 03 medical and health sciences, 0302 clinical medicine, In vitro model, In vivo, Cell adhesion molecule, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cell adhesion, Molecular Biology, Tight junction, Cells, Cultured, 030304 developmental biology, Inflammation, 0303 health sciences, Microcirculation, Soluble cell adhesion molecules, Cell Biology, Coculture, Coculture Techniques, Capillaries, Cell biology, Endothelial stem cell, medicine.anatomical_structure, Blood-Brain Barrier, Cerebrovascular Circulation, Models, Animal, Immunology, Endothelium, Vascular, BBB, Neuroglia, 030217 neurology & neurosurgery
Abstract

Comment in : Technical caveats in identifying the source of endothelial cells in cultures derived from brain microvessels. [Lab Invest. 2005]; International audience; Although cerebral endothelium disturbance is commonly observed in central nervous system (CNS) inflammatory pathologies, neither the cause of this phenomenon nor the effective participation of blood- brain barrier (BBB) in such diseases are well established. Observations were mostly made in vivo using mouse models of chronic inflammation. This paper presents a new mouse in vitro model suitable for the study of underlying mechanistic events touching BBB functions during CNS inflammatory disturbances. This model consists of a coculture with both primary cell types isolated from mice. Mouse brain capillary endothelial cell (MBCEC)s coming from brain capillaries are in culture with their in vivo partners and form differentiated monolayers that retain endothelial markers and numerous phenotypic properties of in vivo cerebral endothelium, such as: (1) peripheral distribution of tight junction proteins (occludin, claudin-5, claudin-3 and JAM-1); (2) high trans-endothelium electrical resistance value; (3) attenuated paracellular flux of sucrose and inulin; (4) P-gp expression; (5) no MECA-32 expression. Furthermore, this endothelium expresses cell adhesion molecules described in vivo and shows intracellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 upregulation under lipopolysaccharide-treatment. Therefore, this well-differentiated model using autologous cells appears as a suitable support to reconstitute pathological in vitro BBB model.

Published
2005

7. Survival of taylorellae in the environmental amoeba Acanthamoeba castellanii

Author

Julie Allombert, Anne Vianney, Sandrine Petry, Laurent Hébert, Claire Laugier, BMC, Ed., Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS 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), Laboratoire d'études et de recherches en pathologie équine, Agence Française de Sécurité Sanitaire des Aliments (AFSSA), JA was supported by a PhD fellowship from the French Ministry of Higher Education and Research. This work was supported by grants from the European Regional Development Fund and by the Basse-Normandie Regional Council (http://www.cr-basse-normandie.fr)., Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Microbiology (medical), food.ingredient, Virulence, Microbiology, Amoeba (genus), 03 medical and health sciences, food, Phagocytosis, Contagious equine metritis, Taylorella asinigenitalis, medicine, Taylorella, Taylorella equigenitalis, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, 0303 health sciences, Acanthamoeba castellanii, Endosymbiont, Microbial Viability, biology, 030306 microbiology, biology.organism_classification, medicine.disease, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Endometritis, Research Article
Abstract

International audience; Background Taylorella equigenitalis is the causative agent of contagious equine metritis, a sexually-transmitted infection of Equidae characterised in infected mares by abundant mucopurulent vaginal discharge and a variable degree of vaginitis, cervicitis or endometritis, usually resulting in temporary infertility. The second species of the Taylorella genus, Taylorella asinigenitalis, is considered non-pathogenic, although mares experimentally infected with this bacterium can develop clinical signs of endometritis. To date, little is understood about the basic molecular virulence and persistence mechanisms employed by the Taylorella species. To clarify these points, we investigated whether the host-pathogen interaction model Acanthamoeba castellanii was a suitable model for studying taylorellae.ResultsWe herein demonstrate that both species of the Taylorella genus are internalised by a mechanism involving the phagocytic capacity of the amoeba and are able to survive for at least one week inside the amoeba. During this one-week incubation period, taylorellae concentrations remain strikingly constant and no overt toxicity to amoeba cells was observed.ConclusionsThis study provides the first evidence of the capacity of taylorellae to survive in a natural environment other than the mammalian genital tract, and shows that the alternative infection model, A. castellanii, constitutes a relevant alternative system to assess host-pathogen interactions of taylorellae. The survival of taylorellae inside the potential environmental reservoir A. castellanii brings new insight, fostering a broader understanding of taylorellae biology and its potential natural ecological niche.

Published
2014

8. Carbon monoxide: mechanisms of action and potential clinical implications

Author

Luc Rochette, Catherine Vergely, Yves Cottin, Marianne Zeller, Laboratoire de Physiopathologie et Pharmacologie Cardio-Métaboliques (U866, Lipides et nutrition, équipe 5) (LPPCM), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, This work was supported by grants from the French Ministry of Research, from the Regional Council of Burgundy and from the Association de Cardiologie de Bourgogne, Physiopathologie et épidémiologie cérébro-cardiovasculaire [Dijon] (PEC2), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC), 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)-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), Vergely, Catherine, Laboratoire de Physiopathologie et Pharmacologie Cardio-Métaboliques (U866, Lipides et nutrition, équipe 5) ( LPPCM ), Lipides - Nutrition - Cancer (U866) ( LNC ), and 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 ) -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 )

Subjects
Carbonate radical, Inflammation, Heme, 030204 cardiovascular system & hematology, medicine.disease_cause, Nitric Oxide, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Sepsis, medicine, Transcription factors, Animals, Humans, Pharmacology (medical), NRF1, CO-RMs, Carbon monoxide, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, 0303 health sciences, Catabolism, CO-releasing molecules, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Transplantation, Vasodilation, chemistry, Biochemistry, Cardiovascular Diseases, Endothelium, Vascular, medicine.symptom, Oxidative stress, Peroxynitrite, Heme Oxygenase-1
Abstract

International audience; Small amounts of carbon monoxide (CO) are continuously produced in mammals. The intracellular levels of CO can increase under stressful conditions following the induction of HO-1 (heme oxygnase-1), a ubiquitous enzyme responsible for the catabolism of heme. Unlike nitric oxide, which is a free radical, CO does not contain free electrons but may be involved in oxidative stress. The carbonate radical has been proposed to be a key mediator of oxidative damage resulting from peroxynitrite production, likewise, the precursor of the carbonate radical anion being bicarbonate and carbon dioxide. We report herein some of the transcription factors and protein kinases involved in the regulation of vascular HO-1 expression. Beyond its widely feared toxicity, CO has revealed a very important biological activity as a signaling molecule with marked protective actions namely against apoptosis and endothelial oxidative damage. Abnormal metabolism and function of CO contribute to the pathogenesis and development of cardiovascular diseases. Important results have been reported in which CO and CO-releasing molecules (CO-RMs) prevent intimal hyperplasia by arresting hyperproliferative vascular smooth muscle cells and increased mobilization and recruitment of bone-marrow-derived progenitor cells. Clinical studies have demonstrated beneficial properties of CO-RMs in transplantation. The anti-inflammatory properties of CO and CO-RMs have been demonstrated in a multitude of animal models of inflammation, suggesting a possible therapeutic application for inflammatory diseases. The development of a technology concerning CO-RMs that controls the delivery and action of CO under different pathological conditions represents a major step forward in the development of CO-based pharmaceuticals with therapeutic applications.

Published
2013

9. Eye-catching odors: olfaction elicits sustained gazing to faces and eyes in 4-month-old infants

Author

Durand, Karine, Baudouin, Jean Yves, Lewkowicz, David, Goubet, Nathalie, Schaal, Benoist, Reid, Vincent, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Dept Psychol, Florida Atlantic University [Boca Raton], This work was financially supported by the Centre National de la Recherche Scientifique, Paris, the French National Agency for Research, the Regional Council of Burgundy, Dijon (PARI grant), and the Institut Universitaire de France (to JYB)., Développement, Individu, Processus, Handicap, Éducation (DIPHE), Université Lumière - Lyon 2 (UL2), Gettysburg College, Department of Communication Sciences & Disorders, Northeastern University [Boston], Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), and Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)

Subjects
Male, newborns, genetic structures, Contextual effects, Visual System, MESH : Research Areas: Science & Technology - Other Topics, Audiology, Eye, Social and Behavioral Sciences, MESH: Web of Science Categories: Multidisciplinary Sciences, 0302 clinical medicine, Psychology, memory retrieval, Attention, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, facial features, MESH : Web of Science Categories: Multidisciplinary Sciences, 05 social sciences, Body odors, Sensory Systems, Smell, Mental Health, visual preference, Alimentation et Nutrition, [SCCO.PSYC]Cognitive science/Psychology, mothers face, Medicine, Female, Sensory Perception, 3-month-old infants, Research Article, medicine.medical_specialty, Science, MESH: Research Areas: Science & Technology - Other Topics, Mothers, 5-month-old infants, Social attention, Olfaction, Biology, Affect (psychology), 050105 experimental psychology, [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, 03 medical and health sciences, developmental-changes, medicine, Humans, Food and Nutrition, 0501 psychology and cognitive sciences, Computational Neuroscience, young infant, mother face, 5-month-old infant, facial feature, developmental-change, 3-month-old infant, schematic face, newborn, Infant, Computational Biology, Gaze, schematic faces, eye diseases, Odor, Odorants, Developmental Psychology, young infants, 030217 neurology & neurosurgery, Photic Stimulation, Neuroscience
Abstract

WOS: 000323733800002; International audience; This study investigated whether an odor can affect infants' attention to visually presented objects and whether it can selectively direct visual gaze at visual targets as a function of their meaning. Four-month-old infants (n = 48) were exposed to their mother's body odors while their visual exploration was recorded with an eye-movement tracking system. Two groups of infants, who were assigned to either an odor condition or a control condition, looked at a scene composed of still pictures of faces and cars. As expected, infants looked longer at the faces than at the cars but this spontaneous preference for faces was significantly enhanced in presence of the odor. As expected also, when looking at the face, the infants looked longer at the eyes than at any other facial regions, but, again, they looked at the eyes significantly longer in the presence of the odor. Thus, 4-month-old infants are sensitive to the contextual effects of odors while looking at faces. This suggests that early social attention to faces is mediated by visual as well as non-visual cues.

Published
2013

10. HMGB-1 promotes fibrinolysis and reduces neurotoxicity mediated by tissue plasminogen activator

Author

Jérôme Parcq, Heikki Rauvala, Maxime Culot, Benoit D. Roussel, Denis Vivien, Amandine Jullienne, Yannick Hommet, Caroline Mysiorek, Ari Rouhiainen, Vincent Berezowski, Carine Ali, Roméo Cecchelli, Roussel, Benoit, Centre-Imagerie, Neurosciences, et Application aux Pathologies (CI-NAPS - UMR 6232), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sérine protéases et physiopathologie de l'unité neurovasculaire, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA), HiLIFE - Neuroscience Center (NC), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, This work was supported by grants from the INSERM, the FrenchMinistry of Research and Technology, the Regional Council of LowerNormandy, the Fondation pour la Recherche Médicale and the Universityof Caen Basse-Normandie, and the conseil régional du Nord-Pas-deCalais(fellowship to C.M.)., and University of Helsinki-University of Helsinki

Subjects
Plasmin, medicine.medical_treatment, MESH: Neurons, MESH: Rats, Sprague-Dawley, Pharmacology, Tissue plasminogen activator, MESH: Fibrinolysis, Rats, Sprague-Dawley, MESH: Blood-Brain Barrier, MESH: Recombinant Proteins, Mice, 0302 clinical medicine, MESH: HMGB1 Protein, MESH: Tissue Plasminogen Activator, MESH: Animals, HMGB1 Protein, Receptor, Cells, Cultured, Neurons, 0303 health sciences, integumentary system, Fibrinolysis, Thrombolysis, MESH: Neuroprotective Agents, Recombinant Proteins, 3. Good health, MESH: N-Methylaspartate, MESH: Cattle, Cytokine, Neuroprotective Agents, Blood-Brain Barrier, HMG-Box Domains, Tissue Plasminogen Activator, MESH: Calcium, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.drug, MESH: Cells, Cultured, N-Methylaspartate, MESH: Rats, Ischemia, Biology, MESH: Coculture Techniques, 03 medical and health sciences, MESH: HMG-Box Domains, medicine, Animals, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Mice, 030304 developmental biology, MESH: Humans, Neurotoxicity, Cell Biology, medicine.disease, Coculture Techniques, Rats, Immunology, MESH: Biomarkers, Calcium, Cattle, 030217 neurology & neurosurgery, Biomarkers
Abstract

International audience; Owing to its ability to generate the clot-dissolving protease plasmin, tissue plasminogen activator (tPA) is the only approved drug for the acute treatment of ischemic stroke. However, tPA also promotes hemorrhagic transformation and excitotoxic events. High mobility group box-1 protein (HMGB-1) is a non-histone transcription factor and a pro-inflammatory cytokine, which has also been shown to bind to both tPA and plasminogen. We thus investigated the cellular and molecular effects through which HMGB-1 could influence the vascular and parenchymal effects of tPA during ischemia. We demonstrate that HMGB-1 not only increases clot lysis by tPA, but also reduces the passage of vascular tPA across the blood-brain barrier, as well as tPA-driven leakage of the blood-brain barrier. In addition, HMGB-1 prevents the pro-neurotoxic effect of tPA, by blocking its interaction with N-methyl-D-aspartate (NMDA) receptors and the attendant potentiation of NMDA-induced neuronal Ca²⁺ influx. In conclusion, we show in vitro that HMGB-1 can promote the beneficial effects of tPA while counteracting its deleterious properties. We suggest that derivatives of HMGB-1, devoid of pro-inflammatory properties, could be used as adjunctive therapies to improve the overall benefit of tPA-mediated thrombolysis following stroke.

Published
2011

11. Gene profiling in white blood cells predicts infliximab responsiveness in rheumatoid arthritis

Author

Anne-Christine Gauthier-Jauneau, Alain Daragon, Martine Hiron, Céline Derambure, François Tron, Jean-Philippe Salier, Maryvonne Daveau, Carine Bansard, Xavier Le Loët, Othmane Mejjad, Olivier Vittecoq, Thierry Lequerré, Service de rhumatologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Protéines de défense des réponses immune et inflammatoire : identification, régulation et rôles physiopathologiques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23), Normandie Université (NU)-Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Centre National de la Recherche Scientifique (CNRS), Consortium EGERIE, CB is the recipient of a fellowship from the French Ministry for Research. This work was supported in part by a grant from Conseil Régional de Haute-Normandie (France)., Maylin, Françoise, Unité de Recherches sur la Génétique des Protéines Humaines [Bois-Guillaume] (U78 INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-CHU Rouen, and Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Oncology, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Time Factors, Microarray, [SDV.GEN] Life Sciences [q-bio]/Genetics, Monocytes, Arthritis, Rheumatoid, 0302 clinical medicine, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, Oligonucleotide Array Sequence Analysis, 0303 health sciences, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antibodies, Monoclonal, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Middle Aged, 3. Good health, Treatment Outcome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antirheumatic Agents, Rheumatoid arthritis, Female, Tumor necrosis factor alpha, Research Article, medicine.drug, Adult, medicine.medical_specialty, Immunology, Peripheral blood mononuclear cell, 03 medical and health sciences, Rheumatology, Predictive Value of Tests, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal medicine, medicine, Humans, RNA, Messenger, Aged, 030304 developmental biology, 030203 arthritis & rheumatology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Tumor Necrosis Factor-alpha, Microarray analysis techniques, business.industry, Gene Expression Profiling, medicine.disease, Infliximab, Methotrexate, business, Follow-Up Studies
Abstract

As indicators of responsiveness to a tumour necrosis factor (TNF)alpha blocking agent (infliximab) are lacking in rheumatoid arthritis, we have used gene profiling in peripheral blood mononuclear cells to predict a good versus poor response to infliximab. Thirty three patients with very active disease (Disease Activity Score 28 >5.1) that resisted weekly methotrexate therapy were given infliximab at baseline, weeks 2 and 6, and every 8th week thereafter. The patients were categorized as responders if a change of Disease Activity Score 28 = 1.2 was obtained at 3 months. Mononuclear cell RNAs were collected at baseline and at three months from responders and non-responders. The baseline RNAs were hybridised to a microarray of 10,000 non-redundant human cDNAs. In 6 responders and 7 non-responders, 41 mRNAs identified by microarray analysis were expressed as a function of the response to treatment and an unsupervised hierarchical clustering perfectly separated these responders from non-responders. The informativeness of 20 of these 41 transcripts, as measured by qRT-PCR, was re-assessed in 20 other patients. The combined levels of these 20 transcripts properly classified 16 out of 20 patients in a leave-one-out procedure, with a sensitivity of 90% and a specificity of 70%, whereas a set of only 8 transcripts properly classified 18/20 patients. Trends for changes in various transcript levels at three months tightly correlated with treatment responsiveness and a down-regulation of specific transcript levels was observed in non-responders only. Our gene profiling obtained by a non-invasive procedure should now be used to predict the likely responders to an infliximab/methotrexate combination.

Published
2006

12. Differential expression of selectins by mouse brain capillary endothelial cells in vitro in response to distinct inflammatory stimuli

Author

Roméo Cecchelli, Caroline Coisne, Yannick Delplace, Bénédicte Dehouck, Lucie Dehouck, Christelle Faveeuw, Florence Miller, Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université d'Artois (UA), CELLIAL Technologies, This work was supported by grants from the Ministry of Research of France (fellowship to C. Coisne) and by the 'Conseil Régional du Nord-Pas-de-Calais' (fellowship to F. Miller)., and We are very grateful to Pr B. Engelhardt (Theodor Kocher Institute, University of Bern, Switzerland) and Dr. J. Boucraut (Laboratoire NICN UMR 6184, Faculté de Médecine Timone, Marseille) to their generous gifts of Abs. The authors thank Dr. Valérie Buée for the critical reading of the manuscript.

Subjects
Lipopolysaccharides, MESH: Cell Adhesion Molecules/metabolism, medicine.medical_treatment, MESH: Lipopolysaccharides/pharmacology, MESH: Neuroglia/drug effects, Fluorescent Antibody Technique, MESH: Animals, Newborn, Mice, 0302 clinical medicine, MESH: Flow Cytometry/methods, MESH: Animals, MESH: Platelet Endothelial Cell Adhesion Molecule-1/metabolism, Cells, Cultured, Cerebral Cortex, 0303 health sciences, biology, MESH: Fluorescent Antibody Technique/methods, Cell adhesion molecule, MESH: Inflammation/chemically induced, General Neuroscience, MESH: Vascular Cell Adhesion Molecule-1/metabolism, MESH: Selectins/metabolism, Flow Cytometry, Intercellular Adhesion Molecule-1, Cell biology, MESH: Cytokines/pharmacology, Endothelial stem cell, Platelet Endothelial Cell Adhesion Molecule-1, Cytokine, medicine.anatomical_structure, Syngenic, Cytokines, medicine.symptom, Neuroglia, Selectin, MESH: Cells, Cultured, MESH: Inflammation/metabolism, MESH: Neuroglia/metabolism, MESH: Cerebral Cortex/cytology, MESH: Endothelial Cells/drug effects, In vitro studies, Vascular Cell Adhesion Molecule-1, Inflammation, Blood–brain barrier, MESH: Endothelial Cells/metabolism, 03 medical and health sciences, E- and P-selectin expression at the blood-brain barrier, Antigens, CD, E-selectin, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: Antigens, CD/metabolism, Endothelial Cells, MESH: Gene Expression Regulation/physiology, MESH: Gene Expression Regulation/drug effects, MESH: Intercellular Adhesion Molecule-1/metabolism, Animals, Newborn, Gene Expression Regulation, Immunology, biology.protein, Selectins, Cell Adhesion Molecules, 030217 neurology & neurosurgery
Abstract

International audience; Increased lymphocyte trafficking across blood-brain barrier (BBB) is a prominent and early event in inflammatory and immune-mediated CNS diseases. The adhesion molecules that control the entry of leukocytes into the brain have not been fully elucidated. Although the role of ICAM-1 and VCAM-1 has been well documented, the expression and role of selectins is still a matter of controversy. In a mouse syngenic in vitro BBB model, highly relevant for examining immunological events, mouse brain capillary endothelial cells (MBCECs) do not express selectins. Treatment of MBCECs with LPS, induced E- and P-selectin expression, whereas TNF-alpha or IFN-gamma treatments did not. Finally, P-selectin but not E-selectin expression was induced in IL-1beta treated MBCECs. Thus, our study suggests that diverse inflammatory stimuli could differentially regulate selectin expression at the BBB.

Published
2005

13. The absence of reactive oxygen species production protects mice against bleomycin-induced pulmonary fibrosis

Author

C. Bertrand, Elisabeth Boichot, Jean-Michel Planquois, Vincent Lagente, Soazig Nenan, Olivier Leclerc, Isabelle Guenon, Boris Manoury, Détoxication et réparation tissulaire, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), R&D, centre de Fresnes, Pfizer, This work is supported by a research grant (ref #2004797) from Conseil Régional de Bretagne and by a collaborative project INSERM/FIOCRUZ., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Maylin, Françoise

Subjects
Pathology, Pulmonary Fibrosis, MESH: Research Support, Non-U.S. Gov't, MESH: Mice, Knockout, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Mice, chemistry.chemical_compound, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Pulmonary fibrosis, MESH: Animals, Lung, Mice, Knockout, chemistry.chemical_classification, 0303 health sciences, MESH: Cytokines, NADPH oxidase, medicine.diagnostic_test, biology, Chemistry, MESH: Reactive Oxygen Species, respiratory system, MESH: Bleomycin, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cytokines, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Bleomycin, MESH: Phosphoproteins, 03 medical and health sciences, Hydroxyproline, MESH: Mice, Inbred C57BL, Internal medicine, medicine, Animals, MESH: Lung, MESH: Mice, 030304 developmental biology, lcsh:RC705-779, Reactive oxygen species, MESH: Pulmonary Fibrosis, Research, NADPH Oxidases, lcsh:Diseases of the respiratory system, Phosphoproteins, medicine.disease, respiratory tract diseases, Mice, Inbred C57BL, MESH: Cytoprotection, Bronchoalveolar lavage, Endocrinology, Cytoprotection, biology.protein, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Reactive Oxygen Species
Abstract

Background Reactive oxygen species and tissue remodeling regulators, such as metalloproteinases (MMPs) and their inhibitors (TIMPs), are thought to be involved in the development of pulmonary fibrosis. We investigated these factors in the fibrotic response to bleomycin of p47phox -/- (KO) mice, deficient for ROS production through the NADPH-oxidase pathway. Methods Mice are administered by intranasal instillation of 0.1 mg bleomycin. Either 24 h or 14 days after, mice were anesthetized and underwent either bronchoalveolar lavage (BAL) or lung removal. Results BAL cells from bleomycin treated WT mice showed enhanced ROS production after PMA stimulation, whereas no change was observed with BAL cells from p47phox -/- mice. At day 1, the bleomycin-induced acute inflammatory response (increased neutrophil count and MMP-9 activity in the BAL fluid) was strikingly greater in KO than wild-type (WT) mice, while IL-6 levels increased significantly more in the latter. Hydroxyproline assays in the lung tissue 14 days after bleomycin administration revealed the absence of collagen deposition in the lungs of the KO mice, which had significantly lower hydroxyproline levels than the WT mice. The MMP-9/TIMP-1 ratio did not change at day 1 after bleomycin administration in WT mice, but increased significantly in the KO mice. By day 14, the ratio fell significantly from baseline in both strains, but more in the WT than KO strains. Conclusions These results suggest that NADPH-oxidase-derived ROS are essential to the development of pulmonary fibrosis. The absence of collagen deposition in KO mice seems to be associated with an elevated MMP-9/TIMP-1 ratio in the lungs. This finding highlights the importance of metalloproteinases and protease/anti-protease imbalances in pulmonary fibrosis.

Published
2005

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