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Is crohn’s disease reversible

Adebowale O Bamidele, Phyllis A Svingen, Mary R Sagstetter, Olga F Sarmento, Michelle Gonzalez, Manuel B Braga Neto, Subra Kugathasan, Gwen Lomberk, Raul A Urrutia, William A Faubion
Background & Aims: Forkhead box protein 3 (FOXP3)+ regulatory T cell (Treg) dysfunction is associated with autoimmune diseases; however, the mechanisms responsible for inflammatory bowel disease pathophysiology are poorly understood. Here, we tested the hypothesis that a physical interaction between transcription factor FOXP3 and the epigenetic enzyme enhancer of zeste homolog 2 (EZH2) is essential for gene co-repressive function. Methods: Human FOXP3 mutations clinically relevant to intestinal inflammation were generated by site-directed mutagenesis...
2019: Cellular and Molecular Gastroenterology and Hepatology
Mei Jiang, Wenhan Huang, Zhongjie Wang, Feifeng Ren, Lei Luo, Jun Zhou, Ruyu Yan, Ning Xia, Lin Tang
Targeting inflammation is considered a challenging pharmacological strategy to prevent or delay the development of inflammatory diseases, such as severe asthma, Crohn's disease, and rheumatoid arthritis. The angiotensin-(1-7) -Mas axis ((Ang-(1-7)-Mas axis) was confirmed to antagonize the effects of the Angiotensin II-AT1 receptor axis and the latter is reported to regulate cardiovascular and renal function, as well as contribute to the inflammatory process. In this paper, we aim to explore the crucial effect of Ang-(1-7) in inflammation and disclose the mechanisms in lipopolysaccharide (LPS)-induced murine macrophages RAW264...
November 17, 2018: Developmental and Comparative Immunology
Elisabeth Hain, Léon Maggiori, Marion Orville, Xavier Tréton, Yoram Bouhnik, Yves Panis
Background & Aims: Faecal diversion (FD) can be proposed in patients with refractory anoperineal Crohn's disease (APCD). This study aimed to assess long-term results of this strategy, following the advent of the anti-TNF era. Methods: All patients who underwent FD for refractory APCD between 2005 and 2017 were included, excluding patients with a history of ileal pouch-anal anastomosis. A multivariate analysis regarding absence of stoma reversal (SR) was performed...
November 19, 2018: Journal of Crohn's & Colitis
Teresa Capriati, Carla Bizzarri, Anna Dilillo, Valerio Nobili, Salvatore Oliva, Antonella Diamanti
Growth failure in children is a frequent feature of childhood-onset Crohn's disease (CD), and stunting can persist into adulthood. Growth is an important outcome by which to judge the effectiveness of therapies in children; currently available studies in CD children have focused on the short-term impact of treatments on growth, and there are limited data regarding the long-term effects of treatments upon growth. Areas covered: We designed the present article to review whether the first treatment performed in newly diagnosed CD children may have a role on the future growth course...
November 7, 2018: Expert Review of Clinical Immunology
Gilles R G Monif
Within the more than one hundred disease entities for which autoimmunity causation have been alleged, two subgroups can be identified. The first group is characterized by ability of disruption of the effector arm of the immune response to temporarily reverse the signs and symptoms of disease. The second group is characterized by the presence of antibodies directed against the target organ's cellular or subcellular components. As long as therapeutic palliation of the signs and symptoms of disease can be achieved, attributing causation to autoimmunity has tended to arrest therapeutics focus on attaining cure...
December 2018: Medical Hypotheses
Bailey Zwarycz, Adam D Gracz, Kristina R Rivera, Ian A Williamson, Leigh A Samsa, Josh Starmer, Michael A Daniele, Luisa Salter-Cid, Qihong Zhao, Scott T Magness
Background & Aims: Crohn's disease is an inflammatory bowel disease that affects the ileum and is associated with increased cytokines. Although interleukin (IL)6, IL17, IL21, and IL22 are increased in Crohn's disease and are associated with disrupted epithelial regeneration, little is known about their effects on the intestinal stem cells (ISCs) that mediate tissue repair. We hypothesized that ILs may target ISCs and reduce ISC-driven epithelial renewal. Methods: A screen of IL6, IL17, IL21, or IL22 was performed on ileal mouse organoids...
2019: Cellular and Molecular Gastroenterology and Hepatology
Avantika Mishra, Darren N Seril
Biological agents are frequently used in the management of inflammatory bowel disease, and it is important to understand the potential adverse effects of these therapies. Ustekinumab is a human monoclonal antibody that interferes with interleukin-12 and -23 cytokine signaling and is approved for the treatment of moderate to severe Crohn's disease. We report 2 cases of neurological adverse events, one of which is consistent with posterior reversible encephalopathy syndrome (PRES), in the setting of ustekinumab therapy for Crohn's disease...
May 2018: Case Reports in Gastroenterology
S Bonnet Ducrot, D Plantaz, N Mathieu, T Debillon, C Bost Bru, M-P Brenier-Pinchart, H Fricker-Hidalgo, M Chevallier
Toxoplasmosis is a potentially serious fetal infection associated with maternal seroconversion of toxoplasmosis during pregnancy. Follow-up and treatment vary between different countries. We present a case of congenital toxoplasmosis with unusual physiopathology and symptomatology. The mother was immunized before the beginning of pregnancy but immunosuppressive treatments for Crohn disease maintained during the pregnancy could explain toxoplasmosis reactivation in the mother and congenital toxoplasmosis. The baby presented reversible B lymphopenia and hypogammaglobulinemia...
October 2018: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
Martin Leutenegger, Ramona Bruckner, Marianne R Spalinger, Silvia Lang, Gerhard Rogler, Michael Scharl
Background: Fistula formation affects up to 50$ of Crohn's disease (CD) patients and causes considerable morbidity. Current pharmacological management mainly includes antibiotics, immunosuppressives, and anti-TNF antibodies. CD fistulas develop from intestinal epithelial cells undergoing epithelial-to-mesenchymal transition (EMT). TGFβ, the most important inducer of EMT, is detectable around CD fistula tracts and induces expression of the EMT-associated transcription factors SNAIL1 and SLUG as well as of IL-13...
July 2018: Inflammatory Intestinal Diseases
Kassem Sharif, Howard Amital, Yehuda Shoenfeld
Autoimmune diseases are a group of heterogeneous condition that occur secondary to the intrinsic loss of tolerance to self- antigens. In genetically susceptible individuals, the complex interplay of environmental factors and epigenetic deregulations have been proposed to drive disease etiopathogenesis. Various environmental variables have been identified including viral infections, exposure to pollutants, stress and dietary factors. Sodium, a major constituent of salt is essential for mammalian physiology. However, high salt intake may play a role in the development of autoimmune diseases...
November 2018: Autoimmunity Reviews
Quinn A Bonafiglia, Sandra R Lourenssen, David J Hurlbut, Michael G Blennerhassett
Inflammation causes proliferation of intestinal smooth muscle cells (ISMC), which contributes to a thickened intestinal wall, and also to stricture formation in Crohn's disease. Proliferation of ISMC both in vitro and in vivo caused decreased expression of marker proteins, but the underlying cause is unclear. Since epigenetic change is important in other systems, we examined this in cell lines from rat colon at either low passage or after extended growth, using immunocytochemistry, immunoblotting and qPCR to evaluate phenotype...
August 15, 2018: American Journal of Physiology. Cell Physiology
Hui-Jing Zhang, Yi-Ning Zhang, Huan Zhou, Lin Guan, Yue Li, Ming-Jun Sun
BACKGROUND: Intestinal fibrosis is a common complication of Crohn's disease (CD). Its exact mechanism is still unclear, and effective treatments to control or reverse the fibrosis process are unavailable. Epithelial-mesenchymal transition (EMT) may promote intestinal fibrosis by increasing deposition of extracellular matrix protein. IL-17A is a pro-inflammatory cytokine, and it has been shown as a profibrotic factor as its association with fibrosis of multiple organs was reported. AIMS: To assess the roles of IL-17A and EMT in the initiation and development of intestinal fibrosis and to verify the potential inductive effect of IL-17A on EMT...
November 2018: Digestive Diseases and Sciences
Kiyoto Mori, Makoto Naganuma, Shinta Mizuno, Hiroaki Suzuki, Mina T Kitazume, Katsuyoshi Shimamura, Sayako Chiba, Akira Sugita, Katsuyoshi Matsuoka, Tadakazu Hisamatsu, Takanori Kanai
Background/Aims: Recent research has highlighted the importance of interactions between commensal fungi and intestinal inflammation. However, there are few studies investigating whether commensal fungi contribute to inflammation in patients with Crohn's disease (CD). The aim of this study is to investigate reveal interactions between commensal fungi and host immune cells in CD. Methods: CD14-positive monocytes were isolated from peripheral blood mononuclear cells from healthy human volunteers and then differentiated in the presence of macrophage colony-stimulating factor (M-CSF) (referred to as M-macrophages, M-Mϕs) or M-CSF and interferon-γ (IFN-γ) (referred to as M-gamma macrophages, Mγ-Mϕs)...
July 2018: Intestinal Research
Eva Karaskova, Jana Volejnikova, Dusan Holub, Maria Velganova-Veghova, Lucie Sulovska, Vladimír Mihal, Monika Horvathova, Dagmar Pospisilova
AIM: Hepcidin is a central regulator of iron homeostasis. Its production is also influenced by systemic inflammation. The aims of this study were to compare hepcidin levels in paediatric patients newly diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) and to determine the association of hepcidin levels with laboratory and clinical parameters of inflammatory bowel disease (IBD) activity. METHODS: Children with newly diagnosed IBD between January 2012 and September 2016 were enrolled in this comparative cross-sectional study...
June 20, 2018: Journal of Paediatrics and Child Health
Ryan Ichikawa, Christopher A Lamb, Jeff Eastham-Anderson, Alexis Scherl, Laura Raffals, William A Faubion, Miriam R Bennett, Anna K Long, John C Mansfield, John A Kirby, Mary E Keir
Background: Recent findings suggest that αE expression is enriched on effector T cells and that intestinal αE+ T cells have increased expression of inflammatory cytokines. αE integrin expression is a potential predictive biomarker for response to etrolizumab, a monoclonal antibody against β7 integrin that targets both α4β7 and αEβ7. We evaluated the prevalence and localization of αE+ cells as well as total αE gene expression in healthy and inflammatory bowel disease patients...
November 9, 2018: Journal of Crohn's & Colitis
Ryoki Takahashi, Takayasu Noguchi, Yoko Mizoguchi, Tadashi Shimoyama, Teruko Nakazawa, Tohru Ikuta
Despite the recent development of biological modifiers for inflammatory bowel diseases (IBD), there continues to be considerable interest in fermented medicines because of its negligible adverse effects. We previously showed that the synbiotic Gut Working Tablet (GWT) alleviates experimental colitis. Here we show that GWT is capable of ameliorating jejunoileal mucosal injury, which is frequently seen with IBD. We created experimental jejunoileal mucositis in rats by injection of methotrexate (MTX) which increases intestinal permeability, a hallmark finding of IBD...
2018: BioMed Research International
Lei Lian, Qunsheng Huang, Longjuan Zhang, Huabo Qin, Xiaosheng He, Xin He, Jia Ke, Minghao Xie, Ping Lan
BACKGROUND: Intestinal fibrosis is a major complication of CD and may result in stricture formation leading to intestinal obstruction. MSCs play multiple roles in active CD and fibrosis-associated diseases. AIMS: This study was designed to investigate the role of MSCs in CD-associated intestinal fibrosis. METHODS: Intestinal fibrosis was induced over 7 weeks of enema with increasing doses of TNBS and assessed by Masson's trichrome staining...
July 2018: Digestive Diseases and Sciences
Jessica R de Bruyn, Gijs R van den Brink, Jessica Steenkamer, Christianne J Buskens, Willem A Bemelman, Sander Meisner, Vanesa Muncan, Anje A Te Velde, Geert R D'Haens, Manon E Wildenberg
Background and Aims: Crohn's disease is a chronic inflammatory disorder of the intestine and often leads to fibrosis, characterized by excess extracellular matrix [ECM] deposition, increased tissue stiffness, and stricture formation. Here we evaluated the contribution of myofibroblast-ECM interactions to the development of intestinal fibrosis in Crohn's disease. Methods: Matched primary human myofibroblasts were isolated from stenotic, inflamed and normal-appearing small intestine within the same Crohn's disease patient [n = 10]...
June 28, 2018: Journal of Crohn's & Colitis
Holger Schäffler, Daniel Pr Herlemann, Paul Klinitzke, Peggy Berlin, Bernd Kreikemeyer, Robert Jaster, Georg Lamprecht
OBJECTIVE: Dysbiosis is a common feature in the pathogenesis of inflammatory bowel diseases (IBD). Environmental factors, such as vitamin D deficiency, seem to play a role in the intestinal inflammation of IBD. The aim of this study was to investigate whether vitamin D administration has an impact on the bacterial composition in Crohn's disease (CD) compared to healthy controls (HC). METHODS: A prospective, longitudinal, controlled interventional analysis was conducted in seven patients with CD in clinical remission and 10 HC to investigate the effect of orally administrated vitamin D on the intestinal bacterial composition using 16S ribosomal RNA gene amplicon sequencing...
April 2018: Journal of Digestive Diseases
Lucas Rodrigues de Carvalho, Tarcisio Vieira de Brito, José Simião da C Júnior, Genilson José Dias Júnior, Diva de Aguiar Magalhãres, Stefany Guimarães Sousa, Renan Oliveira Silva, Felipe Rodolfo Pereira da Silva, Daniel Fernando Pereira Vasconcelos, Leiz Maria Costa Véras, José Roberto de Sousa de Almeida Leite, Dainesy Santos Martins, Conceição da Silva Martins, Jefferson Soares de Oliveira, André Luiz Dos Reis Barbosa
Epiisopiloturine (EPI) is an important imidazole alkaloid because of its pharmacological properties. The aim of this study was to investigate the effects of epiisopiloturine on inflammatory parameters of the colonic mucosa in a rat model of Crohn's disease (CD). For this, we induced colitis using trinitrobenzenosulfonic acid and determined myeloperoxidase (MPO), interleukin 1 β (IL-1β), glutathione (GSH), and malondialdehyde (MDA) levels in the intestinal mucosa. The location and expression of the inflammatory markers in the colon were investigated by immunohistochemistry for NO synthase induced (iNOS), interleukin 1 beta (IL-1β), and cyclooxygenase-2 (COX-2) and western blotting (iNOS and COX-2), respectively...
June 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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