97 results on '"Barreau F"'
Search Results
2. P100 Intestinal epithelial cells under endoplasmic reticulum stress boosts serine proteolytic activity and modulates barrier function
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Solà Tapias, N., Denadai-Souza, A., Rolland-Fourcade, C., Blanpied, C., Dietrich, G., Bonnart, C., Edir, A., Rolland, C., Deraison, C., Vergnolle, N., and Barreau, F.
- Published
- 2017
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3. Long-term alterations of colonic nerve-mast cell interactions induced by neonatal maternal deprivation in rats
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Barreau, F., Salvador-Cartier, C., Houdeau, E., Bueno, L., and Fioramonti, J.
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Animal models in research -- Physiological aspects ,Mast cells -- Physiological aspects ,Maternal deprivation -- Influence ,Maternal deprivation -- Physiological aspects ,Maternal deprivation -- Research ,Irritable bowel syndrome -- Development and progression ,Irritable bowel syndrome -- Models ,Health - Published
- 2008
4. Neonatal maternal deprivation triggers long term alterations in colonic epithelial barrier and mucosal immunity in rats
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Barreau, F., Ferrier, L., Fioramonti, J., and Bueno, L.
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Epithelium -- Health aspects -- Research ,Rats -- Health aspects -- Research ,Rattus -- Health aspects -- Research ,Maternal deprivation -- Risk factors -- Research -- Health aspects ,Stress (Psychology) -- Care and treatment -- Research -- Risk factors ,Health ,Care and treatment ,Research ,Risk factors ,Health aspects - Abstract
Gut 2004;53:501-506. doi: 10.1136/gut.2003.024174 Background: Stressful events in the early period of life (for example, maternal deprivation) have been shown to modify adult immune and gastrointestinal tract functions. The present [...]
- Published
- 2004
5. Influence of sex and experimental protocol on the effect of maternal deprivation on rectal sensitivity to distension in the adult rat
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ROSZTÓCZY, A., FIORAMONTI, J., JÁRMAY, K., BARREAU, F., WITTMANN, T., and BUÉNO, L.
- Published
- 2003
6. Mu and delta opioid receptor knockout mice show increased colonic sensitivity
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Reiss, D., primary, Ceredig, R.A., additional, Secher, T., additional, Boué, J., additional, Barreau, F., additional, Dietrich, G., additional, and Gavériaux-Ruff, C., additional
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- 2016
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7. Impact of anatase and rutile titanium dioxide nanoparticles on uptake carriers and efflux pumps in Caco-2 gut epithelial cells
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Dorier, M., primary, Brun, E., additional, Veronesi, G., additional, Barreau, F., additional, Pernet-Gallay, K., additional, Desvergne, C., additional, Rabilloud, T., additional, Carapito, C., additional, Herlin-Boime, N., additional, and Carrière, M., additional
- Published
- 2015
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8. Mu and delta opioid receptor knockout mice show increased colonic sensitivity.
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Reiss, D., Ceredig, R.A., Secher, T., Boué, J., Barreau, F., Dietrich, G., and Gavériaux ‐ Ruff, C.
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PAIN management ,ANALGESICS ,ANIMAL experimentation ,ANIMALS ,CELL receptors ,COLITIS ,DEXTRAN ,ENKEPHALINS ,INTERLEUKIN-1 ,MICE ,NARCOTICS ,OPIOID peptides ,PAIN ,PROTEIN precursors ,TUMOR necrosis factors ,PHARMACODYNAMICS - Abstract
Background: Opiates act through opioid receptors to diminish pain. Here, we investigated whether mu (MOR) and delta (DOR) receptor endogenous activity assessed in the whole mouse body or in particular at peripheral receptors on primary nociceptive neurons, control colonic pain.Methods: We compared global MOR and DOR receptor knockout (KO) mice, mice with a conditional deletion of MOR and DOR in Nav1.8-positive nociceptive primary afferent neurons (cKO), and control floxed mice of both genders for visceral sensitivity. Visceromotor responses to colorectal distension (CRD) and macroscopic colon scores were recorded on naïve mice and mice with acute colitis induced by 3% dextran sodium sulphate (DSS) for 5 days. Transcript expression for opioid genes and cytokines was measured by quantitative RT-PCR.Results: Naïve MOR and DOR global KO mice show increased visceral sensitivity that was not observed in cKO mice. MOR and preproenkephalin (Penk) were the most expressed opioid genes in colon. MOR KO mice had augmented kappa opioid receptor and Tumour-Necrosis-Factor-α and diminished Penk transcript levels while DOR, preprodynorphin and Interleukin-1β were unchanged. Global MOR KO females had a thicker colon than floxed females. No alteration was detected in DOR mutant animals. A 5-day DSS treatment led to comparable hypersensitivity in the different mouse lines.Conclusion: Our results suggest that mu and delta opioid receptor global endogenous activity but not activity at the peripheral Nav1.8 neurons contribute to visceral sensitivity in naïve mice, and that endogenous MOR and DOR tones were insufficient to elicit analgesia after 5-day DSS-induced colitis.Significance: Knockout mice for mu and delta opioid receptor have augmented colon sensitivity in the CRD assay. It shows endogenous mu and delta opioid analgesia that may be explored as potential targets for alleviating chronic intestinal pain. [ABSTRACT FROM AUTHOR]- Published
- 2017
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9. P057 Influence of colitis on ileal epithelial barrier and its environment in a new mouse model of ulcerative colitis
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Sedghi, S., primary, Tréton, X., additional, Alnabhani, Z., additional, Barreau, F., additional, Cazals-Hatem, D., additional, Pédruzzi, E., additional, Lepage, P., additional, Ogier-Denis, E., additional, and Daniel, F., additional
- Published
- 2014
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10. Intestinal barrier dysfunction triggered by invasive bacteria
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Barreau, F, primary and Hugot, JP, additional
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- 2014
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11. P003 Selective inhibition of eIF2alpha dephosphorylation prevents colitis and shows therapeutic potential in a new model of ulcerative colitis
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Treton, X., primary, Pedruzzi, E., additional, Guichard, C., additional, Vallee, M., additional, Sedghi, S., additional, Ladeiro, Y., additional, Montcuquet, N., additional, Freund, J.N., additional, Van Seuningen, I., additional, Barreau, F., additional, Hugot, J.P., additional, Cazals-Hatem, D., additional, Daniel, F., additional, OgierDenis, E., additional, and Bouhnik, Y., additional
- Published
- 2013
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12. O02 NOD2 REGULATES THE HOST RESPONSE TOWARD MICROFLORA BY MODULATING T-CELL FUNCTION AND EPITHELIAL PERMEABILITY IN MOUSE PEYER'S PATCHES
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Barreau, F., primary, Madre, C., additional, Berrebi, D., additional, Sterkers, G., additional, Bonacorsi, S., additional, Lesuffleur, T., additional, and Hugot, J.P., additional
- Published
- 2009
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13. W1186 CARD15/NOD2 Mediates Susceptibility to Yersinia Pseudotuberculosis
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MEINZER, U, primary, ESMIOLWELTERLIN, S, additional, BARREAU, F, additional, BERREBI, D, additional, DUSSAILLANT, M, additional, BONACORSI, S, additional, CHAREYRE, F, additional, NIWAKAWAKITA, M, additional, ALBERTI, C, additional, and STERKERS, G, additional
- Published
- 2008
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14. Exclusive enteral nutrition enriched with TGF-β restores intestinal homeostasis in a mouse model of Crohn’s disease.
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Boumessid, K., Barreau, F., and Mas, E.
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- 2022
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15. 225. Anisotropic percolation in carbon fiber polymer composites
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Carmona, F., primary, Barreau, F., additional, and Delhaes, P., additional
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- 1982
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16. Percolation in short fibres epoxy resin composites: Conductivity behavior and finite size effects near threshold
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Carmona, F., primary, Prudhon, P., additional, and Barreau, F., additional
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- 1984
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17. An experimental model for studying the effect of anisotropy on percolative conduction
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Carmona, F., primary, Barreau, F., additional, Delhaes, P., additional, and Canet, R., additional
- Published
- 1980
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18. The percolation of fibres with random orientations: a Monte Carlo study
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Boissonade, J, primary, Barreau, F, additional, and Carmona, F, additional
- Published
- 1983
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19. Correction: Perinatal foodborne titanium dioxide exposure-mediated dysbiosis predisposes mice to develop colitis through life.
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Carlé C, Boucher D, Morelli L, Larue C, Ovtchinnikova E, Battut L, Boumessid K, Airaud M, Quaranta-Nicaise M, Ravanat JL, Dietrich G, Menard S, Eberl G, Barnich N, Mas E, Carriere M, Al Nabhani Z, and Barreau F
- Published
- 2024
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20. Perinatal foodborne titanium dioxide exposure-mediated dysbiosis predisposes mice to develop colitis through life.
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Carlé C, Boucher D, Morelli L, Larue C, Ovtchinnikova E, Battut L, Boumessid K, Airaud M, Quaranta-Nicaise M, Ravanat JL, Dietrich G, Menard S, Eberl G, Barnich N, Mas E, Carriere M, Al Nabhani Z, and Barreau F
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- Pregnancy, Female, Animals, Mice, Dysbiosis chemically induced, Lactation, Mice, Inbred C57BL, Disease Models, Animal, Colitis chemically induced, Colitis genetics, Colitis metabolism, Inflammatory Bowel Diseases metabolism
- Abstract
Background: Perinatal exposure to titanium dioxide (TiO
2 ), as a foodborne particle, may influence the intestinal barrier function and the susceptibility to develop inflammatory bowel disease (IBD) later in life. Here, we investigate the impact of perinatal foodborne TiO2 exposure on the intestinal mucosal function and the susceptibility to develop IBD-associated colitis. Pregnant and lactating mother mice were exposed to TiO2 until pups weaning and the gut microbiota and intestinal barrier function of their offspring was assessed at day 30 post-birth (weaning) and at adult age (50 days). Epigenetic marks was studied by DNA methylation profile measuring the level of 5-methyl-2'-deoxycytosine (5-Me-dC) in DNA from colic epithelial cells. The susceptibility to develop IBD has been monitored using dextran-sulfate sodium (DSS)-induced colitis model. Germ-free mice were used to define whether microbial transfer influence the mucosal homeostasis and subsequent exacerbation of DSS-induced colitis., Results: In pregnant and lactating mice, foodborne TiO2 was able to translocate across the host barriers including gut, placenta and mammary gland to reach embryos and pups, respectively. This passage modified the chemical element composition of foetus, and spleen and liver of mothers and their offspring. We showed that perinatal exposure to TiO2 early in life alters the gut microbiota composition, increases the intestinal epithelial permeability and enhances the colonic cytokines and myosin light chain kinase expression. Moreover, perinatal exposure to TiO2 also modifies the abilities of intestinal stem cells to survive, grow and generate a functional epithelium. Maternal TiO2 exposure increases the susceptibility of offspring mice to develop severe DSS-induced colitis later in life. Finally, transfer of TiO2 -induced microbiota dysbiosis to pregnant germ-free mice affects the homeostasis of the intestinal mucosal barrier early in life and confers an increased susceptibility to develop colitis in adult offspring., Conclusions: Our findings indicate that foodborne TiO2 consumption during the perinatal period has negative long-lasting consequences on the development of the intestinal mucosal barrier toward higher colitis susceptibility. This demonstrates to which extent environmental factors influence the microbial-host interplay and impact the long-term mucosal homeostasis., (© 2023. The Author(s).)- Published
- 2023
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21. Proenkephalin deletion in hematopoietic cells induces intestinal barrier failure resulting in clinical feature similarities with irritable bowel syndrome in mice.
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Mas-Orea X, Rey L, Battut L, Bories C, Petitfils C, Abot A, Gheziel N, Wemelle E, Blanpied C, Motta JP, Knauf C, Barreau F, Espinosa E, Aloulou M, Cenac N, Serino M, Mouledous L, Fazilleau N, and Dietrich G
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- Humans, Animals, Mice, Analgesics, Opioid, Enkephalins genetics, Inflammation, Pain, Irritable Bowel Syndrome
- Abstract
Opioid-dependent immune-mediated analgesic effects have been broadly reported upon inflammation. In preclinical mouse models of intestinal inflammatory diseases, the local release of enkephalins (endogenous opioids) by colitogenic T lymphocytes alleviate inflammation-induced pain by down-modulating gut-innervating nociceptor activation in periphery. In this study, we wondered whether this immune cell-derived enkephalin-mediated regulation of the nociceptor activity also operates under steady state conditions. Here, we show that chimeric mice engrafted with enkephalin-deficient bone marrow cells exhibit not only visceral hypersensitivity but also an increase in both epithelial paracellular and transcellular permeability, an alteration of the microbial topography resulting in increased bacteria-epithelium interactions and a higher frequency of IgA-producing plasma cells in Peyer's patches. All these alterations of the intestinal homeostasis are associated with an anxiety-like behavior despite the absence of an overt inflammation as observed in patients with irritable bowel syndrome. Thus, our results show that immune cell-derived enkephalins play a pivotal role in maintaining gut homeostasis and normal behavior in mice. Because a defect in the mucosal opioid system remarkably mimics some major clinical symptoms of the irritable bowel syndrome, its identification might help to stratify subgroups of patients., (© 2023. The Author(s).)
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- 2023
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22. Intestinal involvement in lupus: From pathophysiology to therapeutic perspectives.
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Carlé C, Mas E, and Barreau F
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- Humans, Animals, Mice, Skin pathology, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic drug therapy, Enteritis, Microbiota, Inflammatory Bowel Diseases drug therapy, Inflammatory Bowel Diseases complications
- Abstract
Lupus erythematosus is a complex autoimmune disease characterized by skin and/or systemic involvement. Among systemic disorders, half of the patients will experience non-specific digestive symptoms, usually due to drug medication or transitory infections. In rare cases, lupus enteritis can be observed, and its diagnosis may precede the disease and/or be associated with an inflammatory bowel disease (IBD). Among the underlying mechanisms explaining the digestive damages observed in systemic lupus erythematosus (SLE) and the intestinal barrier function (IBF), increased intestinal permeability, microbiota dysbiosis, and intestinal immune system dysregulations are described in numerous murine and human studies. New therapeutic approaches in addition to conventional treatments are evoked in order to better control the IBF disruption and maybe prevent the onset or worsening of the disease. Thus, the aims of this review are to present the alterations of the digestive tract in SLE patients and the link between SLE and IBD as well as how the different elements of the IBF could participate in SLE pathogenesis.
- Published
- 2023
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23. Relation between auditory difficulties and bortezomib-induced peripheral neuropathy in multiple myeloma: a single-center cross-sectional study.
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Giraudet F, Selvy M, Kerckhove N, Pereira B, Barreau F, Nguyen D, Busserolles J, Cabrespine A, Chaleteix C, Soubrier M, Bay JO, Lemal R, and Balayssac D
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- Bortezomib adverse effects, Cross-Sectional Studies, Humans, Quality of Life, Antineoplastic Agents adverse effects, Multiple Myeloma chemically induced, Multiple Myeloma drug therapy, Peripheral Nervous System Diseases chemically induced, Peripheral Nervous System Diseases drug therapy, Peripheral Nervous System Diseases epidemiology
- Abstract
Purpose: Bortezomib is a neurotoxic drug used in multiple myeloma and responsible for chemotherapy-induced peripheral neuropathy (CIPN). In a previous cross-sectional study, CIPN prevalence was about 26.9% in 67 patients. A second data analysis was performed to explore the relation between CIPN and auditory difficulties., Methods: Based on 66 multiple myeloma patients from a single center, auditory difficulties were assessed with a self-questionnaire and compared to sensory CIPN (QLQ-CIPN20 questionnaire), patients' characteristics and anticancer treatments., Results: The prevalence of auditory difficulties was about 42.4% (95% CI [30.6-55.2]) of the 66 patients analyzed and was higher in patients with CIPN than without (82.4% vs. 28.6%, p < 0.001). Auditory difficulties were not related to the characteristics of patients and treatments. The severity of auditory difficulties were correlated to CIPN severity (spearman's coefficient: 0.49, p = 0.009). Odds-ratio of auditory difficulties (multivariable analysis adjusted for sensory CIPN, recreation or professional noise exposure, gender, age, and treatments) was significantly associated with CIPN (18.7, 95% CI [3.0-117.1], p = 0.002)., Conclusion: This relation between CIPN and auditory difficulties raises concerns about hearing safety in multiple myeloma patients treated by bortezomib., Trial Registration Number: NCT03344328., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
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24. Multi-Omics Analysis of Gut Microbiota in Inflammatory Bowel Diseases: What Benefits for Diagnostic, Prognostic and Therapeutic Tools?
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Lacroix V, Cassard A, Mas E, and Barreau F
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- Bacteria isolation & purification, Disease Progression, Gastrointestinal Microbiome, Humans, Phylogeny, Precision Medicine, Bacteria classification, Inflammatory Bowel Diseases microbiology, Metagenomics methods
- Abstract
Inflammatory bowel diseases (IBDs), which include Crohn's disease and ulcerative colitis, are multifactorial diseases that involve in particular a modification of the gut microbiota, known as dysbiosis. The initial sets of metataxonomic and metagenomic data first made it possible to approximate the microbiota profile in IBD. In addition, today the new 'omics' techniques have enabled us to draw up a functional and integrative map of the microbiota. The key concern in IBD is to develop biomarkers that allow us to assess the activity of the disease and predict the complications and progression, while also guiding the therapeutic care so as to develop personalized medicine. In this review, we present all of the latest discoveries on the microbiota provided by "omics" and we outline the benefits of these techniques in developing new diagnostic, prognostic and therapeutic tools.
- Published
- 2021
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25. Colitis Linked to Endoplasmic Reticulum Stress Induces Trypsin Activity Affecting Epithelial Functions.
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Solà Tapias N, Denadai-Souza A, Rolland-Fourcade C, Quaranta-Nicaise M, Blanpied C, Marcellin M, Edir A, Rolland C, Cirillo C, Dietrich G, Alric L, Portier G, Kirzin S, Bonnet D, Mas E, Burlet-Schiltz O, Deraison C, Bonnart C, Vergnolle N, and Barreau F
- Subjects
- Cell Culture Techniques, Cell Line, Colitis, Ulcerative etiology, Colitis, Ulcerative metabolism, Crohn Disease etiology, Crohn Disease metabolism, Humans, Organoids, Thapsigargin, Colitis, Ulcerative pathology, Crohn Disease pathology, Endoplasmic Reticulum Stress physiology, Enterocytes physiology, Intestinal Absorption physiology, Trypsin metabolism
- Abstract
Background and Aims: Intestinal epithelial cells [IECs] from inflammatory bowel disease [IBD] patients exhibit an excessive induction of endoplasmic reticulum stress [ER stress] linked to altered intestinal barrier function and inflammation. Colonic tissues and the luminal content of IBD patients are also characterized by increased serine protease activity. The possible link between ER stress and serine protease activity in colitis-associated epithelial dysfunctions is unknown. We aimed to study the association between ER stress and serine protease activity in enterocytes and its impact on intestinal functions., Methods: The impact of ER stress induced by Thapsigargin on serine protease secretion was studied using either human intestinal cell lines or organoids. Moreover, treating human intestinal cells with protease-activated receptor antagonists allowed us to investigate ER stress-resulting molecular mechanisms that induce proteolytic activity and alter intestinal epithelial cell biology., Results: Colonic biopsies from IBD patients exhibited increased epithelial trypsin-like activity associated with elevated ER stress. Induction of ER stress in human intestinal epithelial cells displayed enhanced apical trypsin-like activity. ER stress-induced increased trypsin activity destabilized intestinal barrier function by increasing permeability and by controlling inflammatory mediators such as C-X-C chemokine ligand 8 [CXCL8]. The deleterious impact of ER stress-associated trypsin activity was specifically dependent on the activation of protease-activated receptors 2 and 4., Conclusions: Excessive ER stress in IECs caused an increased release of trypsin activity that, in turn, altered intestinal barrier function, promoting the development of inflammatory process., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
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26. Titanium dioxide particles from the diet: involvement in the genesis of inflammatory bowel diseases and colorectal cancer.
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Barreau F, Tisseyre C, Ménard S, Ferrand A, and Carriere M
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- Diet adverse effects, Humans, Intestinal Mucosa, Titanium, Colorectal Neoplasms chemically induced, Colorectal Neoplasms genetics, Inflammatory Bowel Diseases chemically induced, Inflammatory Bowel Diseases genetics
- Abstract
The gastrointestinal tract is a complex interface between the external environment and the immune system. Its ability to control uptake across the mucosa and to protect the body from damage of harmful substances from the lumen is defined as the intestinal barrier function (IBF). The IBF involves four elements: the intestinal microbiota, the mucus layer, the epithelium and the immune system. Its dysfunction is linked with human diseases including inflammatory, metabolic, infectious, autoimmune and neurologic disorders. Most of these diseases are complex and involve genetic, psychological and environmental factors. Over the past 10 years, many genetic polymorphisms predisposing to inflammatory bowel disease (IBD) have been identified. Yet, it is now clear that they are insufficient to explain the onset of these chronic diseases. Although it has been evidenced that some environmental factors such as cigarette smoking or carbohydrate intake are associated with IBD, other environmental factors also present potential health risks such as ingestion of food additives introduced in the human diet, including those composed of mineral particles, by altering the four elements of the intestinal barrier function. The aim of this review is to provide a critical opinion on the potential of TiO
2 particles, especially when used as a food additive, to alter the four elements of the intestinal barrier function, and consequently to evaluate if this additive would likely play a role in the development and/or exacerbation of IBD., (© 2021. The Author(s).)- Published
- 2021
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27. Peripheral Opioid Receptor Blockade Enhances Epithelial Damage in Piroxicam-Accelerated Colitis in IL-10-Deficient Mice.
- Author
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Mas-Orea X, Sebert M, Benamar M, Petitfils C, Blanpied C, Saoudi A, Deraison C, Barreau F, Cenac N, and Dietrich G
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- Animals, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Apoptosis drug effects, Apoptosis genetics, CD4-Positive T-Lymphocytes drug effects, Colitis chemically induced, Colitis genetics, Colitis pathology, Cytokines genetics, Cytokines metabolism, Epithelial Cells drug effects, Inflammation genetics, Inflammation metabolism, Inflammation pathology, Interleukin-10 metabolism, Intestinal Mucosa metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Naloxone pharmacology, Permeability drug effects, Quaternary Ammonium Compounds pharmacology, Severity of Illness Index, Colitis metabolism, Interleukin-10 genetics, Intestinal Mucosa drug effects, Naloxone analogs & derivatives, Narcotic Antagonists administration & dosage, Piroxicam pharmacology, Receptors, Opioid metabolism
- Abstract
Mucosal CD4
+ T lymphocytes display a potent opioid-mediated analgesic activity in interleukin (IL)-10 knockout mouse model of inflammatory bowel diseases (IBD). Considering that endogenous opioids may also exhibit anti-inflammatory activities in the periphery, we examined the consequences of a peripheral opioid receptor blockade by naloxone-methiodide, a general opioid receptor antagonist unable to cross the blood-brain barrier, on the development of piroxicam-accelerated colitis in IL-10-deficient (IL-10-/- ) mice. Here, we show that IL-10-deficient mice treated with piroxicam exhibited significant alterations of the intestinal barrier function, including permeability, inflammation-related bioactive lipid mediators, and mucosal CD4+ T lymphocyte subsets. Opioid receptor antagonization in the periphery had virtually no effect on colitis severity but significantly worsened epithelial cell apoptosis and intestinal permeability. Thus, although the endogenous opioid tone is not sufficient to reduce the severity of colitis significantly, it substantially contributes to the protection of the physical integrity of the epithelial barrier.- Published
- 2021
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28. Bacteria-derived long chain fatty acid exhibits anti-inflammatory properties in colitis.
- Author
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Pujo J, Petitfils C, Le Faouder P, Eeckhaut V, Payros G, Maurel S, Perez-Berezo T, Van Hul M, Barreau F, Blanpied C, Chavanas S, Van Immerseel F, Bertrand-Michel J, Oswald E, Knauf C, Dietrich G, Cani PD, and Cenac N
- Subjects
- Animals, Bacteroidetes, Caco-2 Cells, Cell Membrane Permeability, Chemokine CXCL1 genetics, Colitis chemically induced, Colitis metabolism, Dextran Sulfate, Epithelial Cells physiology, Escherichia coli metabolism, Firmicutes metabolism, Gastrointestinal Microbiome physiology, Gene Expression drug effects, Humans, Interleukin-1beta genetics, Mass Spectrometry, Mice, Oligosaccharides pharmacology, PPAR gamma genetics, Pancreatitis-Associated Proteins genetics, Permeability, Peyer's Patches, Prebiotics, Probiotics chemistry, Stearates analysis, Zonula Occludens-1 Protein genetics, Colitis drug therapy, Intestinal Mucosa metabolism, PPAR gamma metabolism, Stearates metabolism, Stearates therapeutic use
- Abstract
Objective: Data from clinical research suggest that certain probiotic bacterial strains have the potential to modulate colonic inflammation. Nonetheless, these data differ between studies due to the probiotic bacterial strains used and the poor knowledge of their mechanisms of action., Design: By mass-spectrometry, we identified and quantified free long chain fatty acids (LCFAs) in probiotics and assessed the effect of one of them in mouse colitis., Results: Among all the LCFAs quantified by mass spectrometry in Escherichia coli Nissle 1917 (EcN), a probiotic used for the treatment of multiple intestinal disorders, the concentration of 3-hydroxyoctadecaenoic acid (C18-3OH) was increased in EcN compared with other E. coli strains tested. Oral administration of C18-3OH decreased colitis induced by dextran sulfate sodium in mice. To determine whether other bacteria composing the microbiota are able to produce C18-3OH, we targeted the gut microbiota of mice with prebiotic fructooligosaccharides (FOS). The anti-inflammatory properties of FOS were associated with an increase in colonic C18-3OH concentration. Microbiota analyses revealed that the concentration of C18-3OH was correlated with an increase in the abundance in Allobaculum , Holdemanella and Parabacteroides . In culture, Holdemanella biformis produced high concentration of C18-3OH. Finally, using TR-FRET binding assay and gene expression analysis, we demonstrated that the C18-3OH is an agonist of peroxisome proliferator activated receptor gamma., Conclusion: The production of C18-3OH by bacteria could be one of the mechanisms implicated in the anti-inflammatory properties of probiotics. The production of LCFA-3OH by bacteria could be implicated in the microbiota/host interactions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2021
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29. Prevalence of Chemotherapy-Induced Peripheral Neuropathy in Multiple Myeloma Patients and its Impact on Quality of Life: A Single Center Cross-Sectional Study.
- Author
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Selvy M, Kerckhove N, Pereira B, Barreau F, Nguyen D, Busserolles J, Giraudet F, Cabrespine A, Chaleteix C, Soubrier M, Bay JO, Lemal R, and Balayssac D
- Abstract
Bortezomib is a pivotal drug for the management of multiple myeloma. However, bortezomib is a neurotoxic anticancer drug responsible for chemotherapy-induced peripheral neuropathy (CIPN). CIPN is associated with psychological distress and a decrease of health-related quality of life (HRQoL), but little is known regarding bortezomib-related CIPN. This single center, cross-sectional study assessed the prevalence and severity of sensory/motor CIPN, neuropathic pain and ongoing pain medications, anxiety, depression, and HRQoL, in multiple myeloma patients after the end of bortezomib treatment. Paper questionnaires were sent to patients to record the scores of sensory and motor CIPNs (QLQ-CIPN20), neuropathic pain (visual analogue scale and DN4 interview), anxiety and depression (HADS), the scores of HRQoL (QLQ-C30 and QLQ-MY20) and ongoing pain medications. Oncological data were recorded using chemotherapy prescription software and patient medical records. The prevalence of sensory CIPN was 26.9% (95% CI 16.7; 39.1) among the 67 patients analyzed and for a mean time of 2.9 ± 2.8 years since the last bortezomib administration. The proportion of sensory CIPN was higher among patients treated by intravenous and subcutaneous routes than intravenous or subcutaneous routes ( p = 0.003). QLQ-CIPN20 motor scores were higher for patients with a sensory CIPN than those without ( p < 0.001) and were correlated with the duration of treatment and the cumulative dose of bortezomib (coefficient: 0.31 and 0.24, p = 0.01 and 0.0475, respectively), but not sensory scores. Neuropathic pain was screened in 44.4% of patients with sensory CIPN and 66.7% of them had ongoing pain medications, but none were treated with duloxetine (recommended drug). Multivariable analysis revealed that thalidomide treatment (odds-ratio: 6.7, 95% CI 1.3; 35.5, p = 0.03) and both routes of bortezomib administration (odds-ratio: 13.4, 95% CI 1.3; 139.1, p = 0.03) were associated with sensory CIPN. Sensory and motor CIPNs were associated with anxiety, depression, and deterioration of HRQoL. Sensory CIPN was identified in a quarter of patients after bortezomib treatment and associated with psychological distress that was far from being treated optimally. There is a need to improve the management of patients with CIPN, which may include better training of oncologists regarding its diagnosis and pharmacological treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Selvy, Kerckhove, Pereira, Barreau, Nguyen, Busserolles, Giraudet, Cabrespine, Chaleteix, Soubrier, Bay, Lemal and Balayssac.)
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- 2021
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30. How Can a Polymeric Formula Induce Remission in Crohn's Disease Patients?
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Boumessid K, Barreau F, and Mas E
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- Crohn Disease drug therapy, Humans, Intestinal Mucosa drug effects, Intestinal Mucosa pathology, Models, Biological, Remission Induction, Transforming Growth Factor beta2 pharmacology, Transforming Growth Factor beta2 therapeutic use, Crohn Disease pathology, Polymers pharmacology
- Abstract
Crohn's disease is an inflammatory bowel disease whose prevalence is increasing worldwide. Among medical strategies, dietary therapy with exclusive enteral nutrition is recommended as a first-line option, at least for children, because it induces clinical remission and mucosal healing. Modulen
® , a polymeric TGF-β2 enriched formula, has good palatability and is widely used. For the first time in the literature, this review outlines and discusses the clinical outcomes obtained with this therapy, as well as the potential mechanisms of action of its compounds. It can be explained by its TGF-β2 content, but also by its protein and lipid composition. Further well-designed studies are required to improve our knowledge and to optimize therapeutic strategies.- Published
- 2021
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31. Crohn's Disease: Is the Cold Chain Hypothesis Still Hot?
- Author
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Hugot JP, Dumay A, Barreau F, and Meinzer U
- Subjects
- Causality, Crohn Disease genetics, Genetic Predisposition to Disease, Humans, Crohn Disease microbiology, Food Microbiology, Refrigeration, Yersinia pathogenicity
- Abstract
Crohn's disease [CD] is an inflammatory bowel disease of unknown aetiology. During recent decades, significant technological advances led to development of -omic datasets allowing a detailed description of the disease. Unfortunately these have not, to date, resolved the question of the aetiology of CD. Thus, it may be necessary to [re]consider hypothesis-driven approaches to resolve the aetiology of CD. According to the cold chain hypothesis, the development of industrial and domestic refrigeration has led to frequent exposure of human populations to bacteria capable of growing in the cold. These bacteria, at low levels of exposure, particularly those of the genus Yersinia, are believed to be capable of inducing exacerbated inflammation of the intestine in genetically predisposed subjects. We discuss the consistency of this working hypothesis in light of recent data from epidemiological, clinical, pathological, microbiological, and molecular studies., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)
- Published
- 2021
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- View/download PDF
32. [Operation Resilience, care at the crossroads of skills in civil-military cooperation].
- Author
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Barreau F
- Subjects
- Humans, COVID-19 epidemiology, COVID-19 prevention & control, Military Personnel
- Abstract
Launched on 25 March 2020, the operation Resilience is the armed forces' contribution to the interministerial commitment against the spread of COVID-19. The armed forces are committed in all sectors where they can provide support to the civil authorities, adapting their action to local contexts and as part of a permanent dialogue with the state authorities., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
33. Optimization of biologics to reduce treatment failure in inflammatory bowel diseases.
- Author
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Bourchany A, Gilletta De Saint-Joseph C, Breton A, Barreau F, and Mas E
- Subjects
- Drug Monitoring, Drug Resistance, Humans, Treatment Failure, Antibodies, Monoclonal, Humanized therapeutic use, Biological Products therapeutic use, Gastrointestinal Agents therapeutic use, Inflammatory Bowel Diseases drug therapy, Tumor Necrosis Factor-alpha antagonists & inhibitors, Ustekinumab therapeutic use
- Abstract
Moderate to severe inflammatory bowel disease patients can fail to respond to conventional therapy and/or to biologic treatment. In the era of TNFα antagonists and other non-anti-TNF biologic drugs, it is important to review the literature on biologic treatment failure, which could be defined as primary non-response, secondary loss of response and intolerance. Therapeutic drug monitoring (TDM), that is, drug trough level and antidrug antibodies, should enable to determine the mechanisms of treatment failure and to optimize drug efficacy. There is a consensus on reactive TDM at the time of loss of response. Proactive TDM could be of interest during induction and/or maintenance, but randomized controlled trials are required., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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- View/download PDF
34. The Interplay Between Genetic Risk Factors and Proteolytic Dysregulation in the Pathophysiology of Inflammatory Bowel Disease.
- Author
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Solà-Tapias N, Vergnolle N, Denadai-Souza A, and Barreau F
- Subjects
- Gene-Environment Interaction, Genetic Predisposition to Disease, Humans, Pharmacogenetics, Protease Inhibitors pharmacology, Risk Factors, Colitis, Ulcerative drug therapy, Colitis, Ulcerative enzymology, Colitis, Ulcerative genetics, Colitis, Ulcerative immunology, Crohn Disease drug therapy, Crohn Disease enzymology, Crohn Disease genetics, Immunity, Mucosal genetics, Peptide Hydrolases metabolism
- Abstract
Crohn's disease [CD] and ulcerative colitis [UC] are the two main forms of inflammatory bowel disease [IBD]. Previous studies reported increased levels of proteolytic activity in stool and tissue samples from IBD patients, whereas the re-establishment of the proteolytic balance abrogates the development of experimental colitis. Furthermore, recent data suggest that IBD occurs in genetically predisposed individuals who develop an abnormal immune response to intestinal microbes once exposed to environmental triggers. In this review, we highlight the role of proteases in IBD pathophysiology, and we showcase how the main cellular pathways associated with IBD influence proteolytic unbalance and how functional proteomics are allowing the unambiguous identification of dysregulated proteases in IBD, paving the way to the development of new protease inhibitors as a new potential treatment., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
- Full Text
- View/download PDF
35. Nod2 Protects the Gut From Experimental Colitis Spreading to Small Intestine.
- Author
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Al Nabhani Z, Berrebi D, Martinez-Vinson C, Montcuquet N, Madre C, Roy M, Ogier-Denis E, Dussaillant M, Cerf-Bensussan N, Zouali H, Daniel F, Barreau F, and Hugot JP
- Subjects
- Animals, Cecum metabolism, Cecum pathology, Colitis chemically induced, Colitis metabolism, Colitis pathology, Crohn Disease metabolism, Crohn Disease pathology, Duodenitis chemically induced, Duodenitis metabolism, Duodenitis pathology, Duodenum metabolism, Duodenum pathology, Gene Expression, Humans, Ileitis chemically induced, Ileitis metabolism, Ileitis pathology, Ileum metabolism, Ileum pathology, Interferon-gamma metabolism, Interleukin-12 metabolism, Intestinal Mucosa pathology, Mice, Mice, Knockout, Nod2 Signaling Adaptor Protein metabolism, Trinitrobenzenesulfonic Acid, Tumor Necrosis Factor-alpha metabolism, Colitis genetics, Duodenitis genetics, Ileitis genetics, Intestinal Mucosa metabolism, Nod2 Signaling Adaptor Protein genetics, RNA, Messenger metabolism
- Abstract
Background and Aims: Nucleotide oligomerization domain 2 [NOD2] mutations are key risk factors for Crohn's disease [CD]. NOD2 contributes to intestinal homeostasis by regulating innate and adaptive immunity together with intestinal epithelial function. However, the exact roles of NOD2 in CD and other NOD2-associated disorders remain poorly known., Methods: We initially observed that NOD2 expression was increased in epithelial cells away from inflamed areas in CD patients. To explore this finding, Nod2 mRNA expression, inflammation, and cytokines expression were examined in the small bowel of wild-type [WT], Nod2 knockout and Nod2 mutant mice after rectal instillation of 2,4,6-trinitrobenzene sulphonic acid [TNBS]., Results: In WT mice, Nod2 upregulation upstream to rectal injury was associated with pro-inflammatory cytokine expression but no overt histological inflammatory lesions. Conversely, in Nod2-deficient mice the inflammation spread from colitis to ileum and duodenum., Conclusions: Nod2 protects the gut from colitis spreading to small intestine., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2020
- Full Text
- View/download PDF
36. Protease-Activated Receptors in the Intestine: Focus on Inflammation and Cancer.
- Author
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Sébert M, Sola-Tapias N, Mas E, Barreau F, and Ferrand A
- Abstract
Protease-activated receptors (PARs) belong to the G protein-coupled receptor (GPCR) family. Compared to other GPCRs, the specificity of the four PARs is the lack of physiologically soluble ligands able to induce their activation. Indeed, PARs are physiologically activated after proteolytic cleavage of their N-terminal domain by proteases. The resulting N-terminal end becomes a tethered activation ligand that interact with the extracellular loop 2 domain and thus induce PAR signal. PARs expression is ubiquitous and these receptors have been largely described in chronic inflammatory diseases and cancer. In this review, after describing their discovery, structure, mechanisms of activation, we then focus on the roles of PARs in the intestine and the two main diseases affecting the organ, namely inflammatory bowel diseases and cancer., (Copyright © 2019 Sébert, Sola-Tapias, Mas, Barreau and Ferrand.)
- Published
- 2019
- Full Text
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37. Toxicological impact of acute exposure to E171 food additive and TiO 2 nanoparticles on a co-culture of Caco-2 and HT29-MTX intestinal cells.
- Author
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Dorier M, Tisseyre C, Dussert F, Béal D, Arnal ME, Douki T, Valdiglesias V, Laffon B, Fraga S, Brandão F, Herlin-Boime N, Barreau F, Rabilloud T, and Carriere M
- Subjects
- 8-Hydroxy-2'-Deoxyguanosine analysis, Cell Survival drug effects, Coculture Techniques, DNA, Neoplasm drug effects, DNA, Neoplasm genetics, Endoplasmic Reticulum Stress drug effects, Food Additives administration & dosage, Gene Expression Regulation, Neoplastic drug effects, Humans, Oxidative Stress, Particle Size, RNA, Messenger biosynthesis, RNA, Neoplasm biosynthesis, Reactive Oxygen Species metabolism, Tumor Suppressor p53-Binding Protein 1 metabolism, Caco-2 Cells drug effects, Food Additives toxicity, HT29 Cells drug effects, Titanium toxicity
- Abstract
TiO
2 particles are widely used in products for everyday consumption, such as cosmetics and food; their possible adverse effects on human health must therefore be investigated. The aim of this study was to document in vitro impact of the food additive E171, i.e. TiO2 , and of TiO2 nanoparticles, on a co-culture of Caco-2 and HT29-MTX cells, which is an in vitro model for human intestine. Cells were exposed to TiO2 particles three days after seeding, i.e. while they were not fully differentiated. Cell viability, reactive oxygen species (ROS) levels and DNA integrity were assessed, by MTT assay, DCFH-DA assay, alkaline and Fpg-modified comet assay and 8-oxo-dGuo measurement by HPLC-MS/MS. The mRNA expression of genes involved in ROS regulation, DNA repair via base-excision repair, and endoplasmic reticulum stress was assessed by RT-qPCR. Exposure to TiO2 particles resulted in increased intracellular ROS levels, but did not impair cell viability and did not cause any oxidative damage to DNA. Only minor changes in mRNA expression were detected. Altogether, this shows that E171 food additive and TiO2 nanoparticles only produce minor effects to this in vitro intestinal cell model., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2019
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38. Sustainable Positive Response to Sirolimus in Juvenile Polyposis of Infancy.
- Author
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Quaranta M, Laborde N, Ferrand A, Danjoux M, Vergnolle N, Barreau F, Racaud-Sultan C, and Mas E
- Subjects
- Child, Female, Humans, Intestinal Polyposis drug therapy, Treatment Outcome, Immunosuppressive Agents therapeutic use, Intestinal Polyposis congenital, Neoplastic Syndromes, Hereditary drug therapy, Sirolimus therapeutic use
- Published
- 2019
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- View/download PDF
39. NOD2 Expression in Intestinal Epithelial Cells Protects Toward the Development of Inflammation and Associated Carcinogenesis.
- Author
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Ferrand A, Al Nabhani Z, Tapias NS, Mas E, Hugot JP, and Barreau F
- Subjects
- Animals, Carcinogenesis metabolism, Epithelial Cells metabolism, Humans, Inflammation metabolism, Models, Biological, Carcinogenesis pathology, Epithelial Cells pathology, Inflammation pathology, Intestines pathology, Nod2 Signaling Adaptor Protein metabolism
- Abstract
Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular pattern recognition receptor that senses bacterial peptidoglycan-conserved motifs in cytosol and stimulates host immune response including epithelial and immune cells. The association of NOD2 mutations with a number of inflammatory pathologies including Crohn's disease (CD), graft-versus-host diseases, or Blau syndrome, highlights its pivotal role in inflammatory response and the associated-carcinogenesis development. Since its identification in 2001 and its association with CD, the role of NOD2 in epithelial cells and immune cells has been investigated extensively but the precise mechanism by which NOD2 mutations lead to CD and the associated carcinogenesis development is largely unknown. In this review, we present and discuss recent developments about the role of NOD2 inside epithelial cells on the control of the inflammatory process and its linked carcinogenesis development., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
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40. Identification of an analgesic lipopeptide produced by the probiotic Escherichia coli strain Nissle 1917.
- Author
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Pérez-Berezo T, Pujo J, Martin P, Le Faouder P, Galano JM, Guy A, Knauf C, Tabet JC, Tronnet S, Barreau F, Heuillet M, Dietrich G, Bertrand-Michel J, Durand T, Oswald E, and Cenac N
- Subjects
- Analgesics chemistry, Analgesics pharmacology, Animals, Calcium Signaling drug effects, Drug Discovery, Escherichia coli genetics, Genes, Bacterial, Humans, Lipopeptides chemistry, Lipopeptides pharmacology, Male, Mice, Mice, Inbred C57BL, Mutation, Peptides chemistry, Peptides genetics, Peptides metabolism, Polyketides chemistry, Polyketides metabolism, Sensory Receptor Cells drug effects, gamma-Aminobutyric Acid analogs & derivatives, gamma-Aminobutyric Acid chemistry, gamma-Aminobutyric Acid pharmacology, Analgesics metabolism, Escherichia coli metabolism, Lipopeptides biosynthesis, Probiotics metabolism
- Abstract
Administration of the probiotic Escherichia coli strain Nissle 1917 (EcN) decreases visceral pain associated with irritable bowel syndrome. Mutation of clbA, a gene involved in the biosynthesis of secondary metabolites, including colibactin, was previously shown to abrogate EcN probiotic activity. Here, we show that EcN, but not an isogenic clbA mutant, produces an analgesic lipopeptide. We characterize lipoamino acids and lipopeptides produced by EcN but not by the mutant by online liquid chromatography mass spectrometry. One of these lipopeptides, C12AsnGABAOH, is able to cross the epithelial barrier and to inhibit calcium flux induced by nociceptor activation in sensory neurons via the GABA
B receptor. C12AsnGABAOH inhibits visceral hypersensitivity induced by nociceptor activation in mice. Thus, EcN produces a visceral analgesic, which could be the basis for the development of new visceral pain therapies.- Published
- 2017
- Full Text
- View/download PDF
41. Oral Administration of the Probiotic Strain Escherichia coli Nissle 1917 Reduces Susceptibility to Neuroinflammation and Repairs Experimental Autoimmune Encephalomyelitis-Induced Intestinal Barrier Dysfunction.
- Author
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Secher T, Kassem S, Benamar M, Bernard I, Boury M, Barreau F, Oswald E, and Saoudi A
- Abstract
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) with an increasing incidence in developed countries. Recent reports suggest that modulation of the gut microbiota might be one promising therapy for MS. Here, we investigated whether the probiotic Escherichia coli strain Nissle 1917 (ECN) could modulate the outcome of experimental autoimmune encephalomyelitis (EAE), a murine model of MS. We evidenced that daily oral treatment with ECN, but not with the archetypal K12 E. coli strain MG1655, reduced the severity of EAE induced by immunization with the MOG
35-55 peptide. This beneficial effect was associated with a decreased secretion of inflammatory cytokines and an increased production of the anti-inflammatory cytokine IL-10 by autoreactive CD4 T cells, both in peripheral lymph nodes and CNS. Interestingly, ECN-treated mice exhibited increased numbers of MOG-specific CD4+ T cells in the periphery contrasting with severely reduced numbers in the CNS, suggesting that ECN might affect T cell migration from the periphery to the CNS through a modulation of their activation and/or differentiation. In addition, we demonstrated that EAE is associated with a profound defect in the intestinal barrier function and that treatment with ECN, but not with MG1655, repaired intestinal permeability dysfunction. Collectively, our data reveal that EAE induces a disruption of the intestinal homeostasis and that ECN protects from disease and restores the intestinal barrier function.- Published
- 2017
- Full Text
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42. Continuous in vitro exposure of intestinal epithelial cells to E171 food additive causes oxidative stress, inducing oxidation of DNA bases but no endoplasmic reticulum stress.
- Author
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Dorier M, Béal D, Marie-Desvergne C, Dubosson M, Barreau F, Houdeau E, Herlin-Boime N, and Carriere M
- Subjects
- Animals, Caco-2 Cells, Cell Survival drug effects, Coculture Techniques, Comet Assay, Epithelial Cells drug effects, Epithelial Cells metabolism, HT29 Cells, Humans, Ileum drug effects, Ileum metabolism, Models, Biological, Mucus metabolism, Oxidation-Reduction, Oxidative Stress genetics, DNA Damage, Food Additives toxicity, Nanoparticles toxicity, Oxidative Stress drug effects, Titanium toxicity
- Abstract
The whitening and opacifying properties of titanium dioxide (TiO
2 ) are commonly exploited when it is used as a food additive (E171). However, the safety of this additive can be questioned as TiO2 nanoparticles (TiO2 -NPs) have been classed at potentially toxic. This study aimed to shed some light on the mechanisms behind the potential toxicity of E171 on epithelial intestinal cells, using two in vitro models: (i) a monoculture of differentiated Caco-2 cells and (ii) a coculture of Caco-2 with HT29-MTX mucus-secreting cells. Cells were exposed to E171 and two different types of TiO2 -NPs, either acutely (6-48 h) or repeatedly (three times a week for 3 weeks). Our results confirm that E171 damaged these cells, and that the main mechanism of toxicity was oxidation effects. Responses of the two models to E171 were similar, with a moderate, but significant, accumulation of reactive oxygen species, and concomitant downregulation of the expression of the antioxidant enzymes catalase, superoxide dismutase and glutathione reductase. Oxidative damage to DNA was detected in exposed cells, proving that E171 effectively induces oxidative stress; however, no endoplasmic reticulum stress was detected. E171 effects were less intense after acute exposure compared to repeated exposure, which correlated with higher Ti accumulation. The effects were also more intense in cells exposed to E171 than in cells exposed to TiO2 -NPs. Taken together, these data show that E171 induces only moderate toxicity in epithelial intestinal cells, via oxidation.- Published
- 2017
- Full Text
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43. Complementary Roles of Nod2 in Hematopoietic and Nonhematopoietic Cells in Preventing Gut Barrier Dysfunction Dependent on MLCK Activity.
- Author
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Al Nabhani Z, Montcuquet N, Roy M, Dussaillant M, Hugot JP, and Barreau F
- Subjects
- Animals, Caco-2 Cells, Cell Membrane Permeability, Humans, Intestinal Mucosa pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Phosphorylation, Tight Junctions, Hematopoietic Stem Cells metabolism, Intestinal Mucosa metabolism, Myosin-Light-Chain Kinase metabolism, Nod2 Signaling Adaptor Protein physiology, Peyer's Patches metabolism
- Abstract
Background: Crohn's disease (CD) pathogenesis is multifactorial involving genetic and environmental factors. Loss of function mutations in the nucleotide oligomerization domain 2 (NOD2) gene are the main genetic risk factor for CD. Like patients with CD, Nod2 mice are characterized by an enhanced Th1 immune response and a defective mucosal barrier function evidenced by increased intestinal permeability. We previously showed that the latter is related to hematopoietic Nod2 deficiency. Our aim was to explore the mechanisms by which Nod2 expressed in the hematopoietic and in the nonhematopoietic compartments interplay to control epithelial paracellular permeability., Methods: Depletion of CD4 T cells in Nod2 mice and treatments with inhibitors were conducted in chimeric mice transplanted with bone marrow cells from Nod2-deficient donors into Nod2-sufficient recipients or vice versa. Caco-2 cells overexpressing a NOD2 gene which did or did not include a CD-associated polymorphism were treated with inhibitors or siRNAs and cocultured with hematopoietic cells from Peyer's patches., Results: In vivo and in vitro Nod2 in hematopoietic cells regulates epithelial paracellular permeability through cytokine production influencing myosin light chain kinase (MLCK) activity. Indeed, tumor necrosis factor-α and interferon-γ secretion by CD4 T cells upregulated expression and activity of epithelial MLCK leading to increased epithelial tight junction opening. When stimulated by muramyl dipeptide, Nod2 in the nonhematopoietic compartment normalized the permeability and T-cell cytokine secretion and regulated MLCK activity. This MLCK regulation is mediated by TAK1 and RICK-dependent mechanisms., Conclusions: Our study demonstrates how hematopoietic and nonhematopoietic Nod2 regulate intestinal barrier function, improving our knowledge on the mechanisms involved in CD pathogenesis.
- Published
- 2017
- Full Text
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44. Nod2: The intestinal gate keeper.
- Author
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Al Nabhani Z, Dietrich G, Hugot JP, and Barreau F
- Subjects
- Animals, Humans, Gastrointestinal Microbiome immunology, Host-Pathogen Interactions immunology, Intestines immunology, Nod2 Signaling Adaptor Protein immunology
- Abstract
Nucleotide-binding oligomerization domain 2 (NOD2) is an intracellular pattern recognition receptor that senses bacterial peptidoglycan (PGN)-conserved motifs in cytosol and stimulates host immune response. The association of NOD2 mutations with a number of inflammatory pathologies, including Crohn disease (CD), Graft-versus-host disease (GVHD), and Blau syndrome, highlights its pivotal role in host-pathogen interactions and inflammatory response. Stimulation of NOD2 by its ligand (muramyl dipeptide) activates pro-inflammatory pathways such as nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), and Caspase-1. A loss of NOD2 function may result in a failure in the control of microbial infection, thereby initiating systemic responses and aberrant inflammation. Because the ligand of Nod2 is conserved in both gram-positive and gram-negative bacteria, NOD2 detects a wide variety of microorganisms. Furthermore, current literature evidences that NOD2 is also able to control viruses' and parasites' infections. In this review, we present and discuss recent developments about the role of NOD2 in shaping the gut commensal microbiota and pathogens, including bacteria, viruses, and parasites, and the mechanisms by which Nod2 mutations participate in disease occurrence.
- Published
- 2017
- Full Text
- View/download PDF
45. Nod2 Deficiency Leads to a Specific and Transmissible Mucosa-associated Microbial Dysbiosis Which Is Independent of the Mucosal Barrier Defect.
- Author
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Al Nabhani Z, Lepage P, Mauny P, Montcuquet N, Roy M, Le Roux K, Dussaillant M, Berrebi D, Hugot JP, and Barreau F
- Subjects
- Animals, Antimicrobial Cationic Peptides metabolism, Female, Gastrointestinal Microbiome genetics, Intestinal Mucosa metabolism, Intestinal Mucosa microbiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Mucins metabolism, Nod2 Signaling Adaptor Protein physiology, Peyer's Patches physiopathology, RNA, Ribosomal, 16S genetics, Real-Time Polymerase Chain Reaction, Dysbiosis physiopathology, Gastrointestinal Microbiome physiology, Intestinal Mucosa physiopathology, Nod2 Signaling Adaptor Protein deficiency
- Abstract
Background and Aims: Crohn's disease [CD] is a complex disorder characterised by an inappropriate immune response, impaired barrier function and microbial dysbiosis. Mutations in nucleotide oligomeriation domain 2 [NOD2] are CD risk factors. Increase of intestinal permeability, CD4
+ T cell infiltration, and bacterial dysbiosis are also seen in Nod2-knockout [Nod2KO ] mice. However, the specificity and relationship between these Nod2-associated abnormalities remain largely unexplored., Methods: Wild-type [WT], Nod1-knockout [Nod1KO ] and Nod2KO mice were analysed in parallel. Microbial composition was defined by 454-pyrosequencing of bacterial 16S rRNA genes. Mucin and antimicrobial peptide expression was assessed by RT-PCR. Cell populations from Peyer's patches were determined by flow cytometry. Ussing chambers were used to measure intestinal permeability and bacterial translocation. Finally, to explore the impact of colonisation with mother's microbiota at birth, analyses were also performed in Nod2KO and WT mice born from WT surrogate mothers after embryo transfer., Results: Nod2KO mice exhibited colonic bacterial dysbiosis different from WT and Nod1KO mice. Altered expression of antimicrobial peptides and mucins in ileum and colon was associated with the microbial composition. Bacterial composition of Nod2KO and WT mice obtained by embryo transfer was similar to that observed in Nod2KO mice, arguing for a dominant effect of Nod2KO -associated dysbiosis. In contrast, increased levels of CD4+ T cells and gut barrier defects across Peyer's patches were specific to Nod2 deficiency and independent of Microbial dysbiosis., Conclusions: Nod2 deficiency is associated with a specific dominant dysbiosis which does not drive mucosal tissue and immune alterations., (Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)- Published
- 2016
- Full Text
- View/download PDF
46. Increased Proliferation of the Ileal Epithelium as a Remote Effect of Ulcerative Colitis.
- Author
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Sedghi S, Barreau F, Morilla I, Montcuquet N, Cazals-Hatem D, Pedruzzi E, Rannou E, Tréton X, Hugot JP, Ogier-Denis E, and Daniel F
- Subjects
- Animals, Case-Control Studies, Colitis, Ulcerative etiology, Colitis, Ulcerative pathology, Humans, Intestinal Mucosa pathology, MAP Kinase Signaling System physiology, Mice, Mice, Inbred C57BL, Trinitrobenzenesulfonic Acid, Wnt Signaling Pathway physiology, beta Catenin physiology, Cell Proliferation physiology, Colitis, Ulcerative physiopathology, Ileum physiopathology, Intestinal Mucosa physiopathology
- Abstract
Background: Aside from cases of backwash ileitis, the ileal mucosa of patients with ulcerative colitis (UC), an idiotypic inflammatory bowel disease, has received little attention despite the fact that colitis is known to trigger alterations in morphology and/or functions of the small intestine remotely., Methods: The ileal mucosa was studied in patients with UC and in a spontaneous model of colitis (Il10/Nox1 mice) mimicking the histological and clinical features of UC and was also studied in acute and chronic murine models of chemically induced colitis. Proliferation and apoptosis were assessed using morphological and immunohistological methods and Western blot analysis. Peyer's patch immune cell subsets were analyzed. Cytokines levels were quantified using quantitative PCR and Luminex xMAP technology. Total RNA from isolated ileal crypts was used for whole genome transcriptome analysis., Results: The most striking features were an increased ileal crypt length associated with an enhanced cell proliferation of the transit-amplifying cells along with activation of the Wnt/β-catenin and MAPkinase pathways. These changes did not result from intestinal inflammation as assessed by histology and/or pro-inflammatory cytokine expression levels. The increased proliferation rate was dependent on the duration but not on the severity of colitis and was observed in different mouse models of colitis, including the Il10/Nox1 model and 2,4,6-trinitrobenzenesulfonic acid-treated mice. Interestingly, the ileal mucosa of patients with UC also displayed longer crypts and enhanced cell proliferation compared with control patients., Conclusions: These data show that despite the absence of inflammation in the small intestine, alterations in the ileal mucosa homeostasis are present in UC.
- Published
- 2016
- Full Text
- View/download PDF
47. Respective Roles of Hematopoietic and Nonhematopoietic Nod2 on the Gut Microbiota and Mucosal Homeostasis.
- Author
-
Alnabhani Z, Hugot JP, Montcuquet N, Le Roux K, Dussaillant M, Roy M, Leclerc M, Cerf-Bensussan N, Lepage P, and Barreau F
- Subjects
- Animals, Dysbiosis metabolism, Dysbiosis pathology, Hematopoietic Stem Cells metabolism, Intestinal Mucosa metabolism, Mice, Mice, Knockout, Dysbiosis microbiology, Gastrointestinal Microbiome, Hematopoietic Stem Cells microbiology, Homeostasis physiology, Intestinal Mucosa microbiology, Nod2 Signaling Adaptor Protein physiology
- Abstract
Background: NOD2 mutations are associated with Crohn's disease (CD). Both CD (in human) and Nod2 deficiency (in mice) are characterized by increased mucosal CD4 T-cells, an altered permeability and a microbial dysbiosis. However, the respective roles of the gut epithelial and immune compartments on the phenotype are not known., Methods: Microbial composition, epithelial peptide secretion, intestinal permeability, and immune cell composition of Peyer patches were studied in Nod2 knock-out mice transplanted with wild-type bone marrow cells and vice versa., Results: The nonhematopoietic cells control the microbiota composition and epithelial secretion of mucins and antimicrobial peptides. These parameters are correlated with recurrent associations between bacterial species and luminal products. In contrast, Nod2 in the hematopoietic compartment regulates the epithelial permeability and the gut-associated lymphoid tissue independently of the bacterial composition., Conclusions: The immune system and the gut permeability in one hand and the microbial and epithelial peptide compositions in the other hand are separate couples of interdependent parameters, both controlled by Nod2 in either the hematopoietic or nonhematopoietic lineages.
- Published
- 2016
- Full Text
- View/download PDF
48. Pseudomonas fluorescens alters the intestinal barrier function by modulating IL-1β expression through hematopoietic NOD2 signaling.
- Author
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Alnabhani Z, Montcuquet N, Biaggini K, Dussaillant M, Roy M, Ogier-Denis E, Madi A, Jallane A, Feuilloley M, Hugot JP, Connil N, and Barreau F
- Subjects
- Animals, Blotting, Western, Caco-2 Cells, Cell Membrane Permeability, Cells, Cultured, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells microbiology, Humans, Interleukin-1beta genetics, Interleukin-1beta metabolism, Intestinal Mucosa cytology, Intestinal Mucosa microbiology, Macrophages cytology, Macrophages microbiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Nod2 Signaling Adaptor Protein genetics, Nod2 Signaling Adaptor Protein metabolism, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Hematopoietic Stem Cells metabolism, Intestinal Mucosa metabolism, Macrophages metabolism, Nod2 Signaling Adaptor Protein physiology, Pseudomonas fluorescens physiology, Receptors, Interleukin-1 physiology
- Abstract
Background: Ileal Crohn's disease is related to NOD2 mutations and to a gut barrier dysfunction. Pseudomonas fluorescens has also been associated with ileal Crohn's disease. The aim of this study was to determine the impact of P. fluorescens on the paracellular permeability in ileum and Peyer's patches., Methods: To explore this question, in vivo and ex vivo experiments were performed in wild-type, Nod2, Nod2, and IL-1R mice together with in vitro analyses using the Caco-2 (epithelial) and the THP-1 (monocyte) human cell lines., Results: Pseudomonas fluorescens increased the paracellular permeability of the intestinal mucosa through the secretion of IL-1β by the immune cell populations and the activation of myosin light chain kinase in the epithelial cells. Induction of the IL-1β pathway required the expression of Nod2 in the hematopoietic compartment, and muramyl dipeptide (a Nod2 ligand) had an inhibitory effect., Conclusions: Pseudomonas fluorescens thus alters the homeostasis of the epithelial barrier function by a mechanism similar to that previously observed for Yersinia pseudotuberculosis. This work further documents a putative role of psychrotrophic bacteria in Crohn's disease.
- Published
- 2015
- Full Text
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49. The laminin response in inflammatory bowel disease: protection or malignancy?
- Author
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Spenlé C, Lefebvre O, Lacroute J, Méchine-Neuville A, Barreau F, Blottière HM, Duclos B, Arnold C, Hussenet T, Hemmerlé J, Gullberg D, Kedinger M, Sorokin L, Orend G, and Simon-Assmann P
- Subjects
- Animals, Caco-2 Cells, Cytokines metabolism, HCT116 Cells, HT29 Cells, Humans, Laminin genetics, Mice, Tumor Suppressor Protein p53 metabolism, Carcinoma metabolism, Colonic Neoplasms metabolism, Inflammatory Bowel Diseases metabolism, Laminin metabolism
- Abstract
Laminins (LM), basement membrane molecules and mediators of epithelial-stromal communication, are crucial in tissue homeostasis. Inflammatory Bowel Diseases (IBD) are multifactorial pathologies where the microenvironment and in particular LM play an important yet poorly understood role in tissue maintenance, and in cancer progression which represents an inherent risk of IBD. Here we showed first that in human IBD colonic samples and in murine colitis the LMα1 and LMα5 chains are specifically and ectopically overexpressed with a concomitant nuclear p53 accumulation. Linked to this observation, we provided a mechanism showing that p53 induces LMα1 expression at the promoter level by ChIP analysis and this was confirmed by knockdown in cell transfection experiments. To mimic the human disease, we induced colitis and colitis-associated cancer by chemical treatment (DSS) combined or not with a carcinogen (AOM) in transgenic mice overexpressing LMα1 or LMα5 specifically in the intestine. We demonstrated that high LMα1 or LMα5 expression decreased susceptibility towards experimentally DSS-induced colon inflammation as assessed by histological scoring and decrease of pro-inflammatory cytokines. Yet in a pro-oncogenic context, we showed that LM would favor tumorigenesis as revealed by enhanced tumor lesion formation in both LM transgenic mice. Altogether, our results showed that nuclear p53 and associated overexpression of LMα1 and LMα5 protect tissue from inflammation. But in a mutation setting, the same LM molecules favor progression of IBD into colitis-associated cancer. Our transgenic mice represent attractive new models to acquire knowledge about the paradoxical effect of LM that mediate either tissue reparation or cancer according to the microenvironment. In the early phases of IBD, reinforcing basement membrane stability/organization could be a promising therapeutic approach.
- Published
- 2014
- Full Text
- View/download PDF
50. Combined NADPH oxidase 1 and interleukin 10 deficiency induces chronic endoplasmic reticulum stress and causes ulcerative colitis-like disease in mice.
- Author
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Tréton X, Pedruzzi E, Guichard C, Ladeiro Y, Sedghi S, Vallée M, Fernandez N, Bruyère E, Woerther PL, Ducroc R, Montcuquet N, Freund JN, Van Seuningen I, Barreau F, Marah A, Hugot JP, Cazals-Hatem D, Bouhnik Y, Daniel F, and Ogier-Denis E
- Subjects
- Animals, Blotting, Western, Case-Control Studies, Cell Proliferation, Cells, Cultured, Colitis, Ulcerative metabolism, Colitis, Ulcerative pathology, Colon immunology, Colon metabolism, Colon pathology, Endoplasmic Reticulum metabolism, Endoplasmic Reticulum pathology, Female, Flow Cytometry, Fluorescent Antibody Technique, Humans, Immunoenzyme Techniques, Inflammation metabolism, Inflammation pathology, Intestinal Mucosa metabolism, Intestinal Mucosa pathology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, NADPH Oxidase 1, Phosphorylation, Protein Phosphatase 1 genetics, Protein Phosphatase 1 metabolism, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Unfolded Protein Response, Colitis, Ulcerative etiology, Disease Models, Animal, Endoplasmic Reticulum Stress, Inflammation etiology, Interleukin-10 physiology, NADH, NADPH Oxidoreductases physiology
- Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the rectum which progressively extents. Its etiology remains unknown and the number of treatments available is limited. Studies of UC patients have identified an unbalanced endoplasmic reticulum (ER) stress in the non-inflamed colonic mucosa. Animal models with impaired ER stress are sensitive to intestinal inflammation, suggesting that an unbalanced ER stress could cause inflammation. However, there are no ER stress-regulating strategies proposed in the management of UC partly because of the lack of relevant preclinical model mimicking the disease. Here we generated the IL10/Nox1dKO mouse model which combines immune dysfunction (IL-10 deficiency) and abnormal epithelium (NADPH oxidase 1 (Nox1) deficiency) and spontaneously develops a UC-like phenotype with similar complications (colorectal cancer) than UC. Our data identified an unanticipated combined role of IL10 and Nox1 in the fine-tuning of ER stress responses in goblet cells. As in humans, the ER stress was unbalanced in mice with decreased eIF2α phosphorylation preceding inflammation. In IL10/Nox1dKO mice, salubrinal preserved eIF2α phosphorylation through inhibition of the regulatory subunit of the protein phosphatase 1 PP1R15A/GADD34 and prevented colitis. Thus, this new experimental model highlighted the central role of epithelial ER stress abnormalities in the development of colitis and defined the defective eIF2α pathway as a key pathophysiological target for UC. Therefore, specific regulators able to restore the defective eIF2α pathway could lead to the molecular remission needed to treat UC.
- Published
- 2014
- Full Text
- View/download PDF
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