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experimental colitis

Jeremy A Goettel, Roopali Gandhi, Jessica E Kenison, Ada Yeste, Gopal Murugaiyan, Sharmila Sambanthamoorthy, Alexandra E Griffith, Bonny Patel, Dror S Shouval, Howard L Weiner, Scott B Snapper, Francisco J Quintana
Existing therapies for inflammatory bowel disease that are based on broad suppression of inflammation result in variable clinical benefit and unwanted side effects. A potential therapeutic approach for promoting immune tolerance is the in vivo induction of regulatory T cells (Tregs). Here we report that activation of the aryl hydrocarbon receptor using the non-toxic agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) induces human Tregs in vitro that suppress effector T cells through a mechanism mediated by CD39 and Granzyme B...
October 25, 2016: Cell Reports
Irene D Román, David Cano-Martínez, María Val T Lobo, María Dolores Fernández-Moreno, Borja Hernández-Breijo, Silvia Sacristán, Patricia Sanmartín-Salinas, Jorge Monserrat, Javier P Gisbert, Luis G Guijarro
: Objetive: Our purpose was to study the molecular basis of infliximab (IFX) effect on colon mucosa in a colitis model and to identify new biomarkers of mucosal healing. METHODS: Healthy rats and rats which were subjected to experimental colitis induced by dextran sulphate sodium, with or without IFX treatment (in the short- and long-term), were studied along with forty-seven IBD patients. Colon mucosal integrity by Periodic Acid Schiff staining, intestinal damage by immunohistochemistry (proliferating cell nuclear antigen, β-catenin, E-cadherin, phosphotyrosine, p-p38, allograft inflammatory factor-1 (AIF-1) and colonic mucosal apoptosis by TUNEL staining were evaluated in rats...
October 26, 2016: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
R F Claudino, D F Leite, A F Bento, J G Chichorro, J B Calixto, G A Rae
OBJECTIVE AND DESIGN: This study attempted to clarify the roles of endothelins and mechanisms associated with ETA/ETB receptors in mouse models of colitis. MATERIALS AND METHODS: Colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 1.5 mg/animal) or dextran sulfate sodium (DSS, 3%). After colitis establishment, mice received Atrasentan (ETA receptor antagonist, 10 mg/kg), A-192621 (ETB receptor antagonist, 20 mg/kg) or Dexamethasone (1 mg/kg) and several inflammatory parameters were assessed, as well as mRNA levels for ET-1, ET-2 and ET receptors...
October 24, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
Daline Fernandes de Souza Araújo, Gerlane Coelho Bernardo Guerra, Raimundo Fernandes de Araújo Júnior, Aurigena Antunes de Araújo, Paloma Oliveira Antonino de Assis, Ariosvaldo Nunes de Medeiros, Yasmim Regis Formiga de Sousa, Maria Manuela Estevez Pintado, Julio Gálvez, Rita de Cássia Ramos do Egypto Queiroga
Complementary or alternative medicine is of great interest for the treatment of inflammatory bowel disease, with the aim of ameliorating the side effects of the drugs commonly used or improving their efficacy. In this study, we evaluated the ability of goat whey to prevent intestinal inflammation in the experimental model of acetic acid-induced rats and compared it to sulfasalazine. Pretreatment with goat whey (1, 2, and 4 g/kg) and sulfasalazine (250 mg/kg) on colitic rats improved colonic inflammatory markers, including myeloperoxidase activity, leukotriene B4 levels, as well as the production of proinflammatory cytokines IL-1β and tumor necrosis factor-α...
October 19, 2016: Journal of Dairy Science
Rocío López-Posadas, Cristina Mascaraque, Raquel González, María D Suárez, Antonio Zarzuelo, Olga Martínez-Augustin, Fermín Sánchez de Medina
BACKGROUND: Statins have antiinflammatory effects at the cardiovascular level because of inhibition of prenylation, which also probably underlies their therapeutic effects in preclinical models of inflammatory bowel disease. Another inhibitor of prenylation, namely alendronate, reduces colitis in rodents. In this study, we aim to explore the therapeutic potential of second-generation, nitrogen-containing bisphosphonates in 3 preclinical models of colitis. METHODS: The trinitrobenzenesulfonic acid and dextran sulfate sodium models of rat colitis and the adoptive lymphocyte transfer model of colitis in mice were used...
November 2016: Inflammatory Bowel Diseases
Ester Pagano, Raffaele Capasso, Fabiana Piscitelli, Barbara Romano, Olga A Parisi, Stefania Finizio, Anna Lauritano, Vincenzo Di Marzo, Angelo A Izzo, Francesca Borrelli
Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for "CBD botanical drug substance," on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil...
2016: Frontiers in Pharmacology
Anna Keppner, Sumedha Malsure, Antoine Nobile, Muriel Auberson, Olivier Bonny, Edith Hummler
BACKGROUND: Inflammatory bowel diseases (IBD) including ulcerative colitis and Crohn's disease are diseases with impaired epithelial barrier function. We aimed to investigate whether mutated prostasin and thus, reduced colonic epithelial sodium channel activity predisposes to develop an experimentally dextran sodium sulfate (DSS)-induced colitis. METHODS: Wildtype, heterozygous (fr/+), and homozygous (fr/fr) prostasin-mutant rats were treated 7 days with DSS followed by 7 days of recovery and analyzed with respect to histology, clinicopathological parameters, inflammatory marker mRNA transcript expression, and sodium transporter protein expression...
October 12, 2016: Inflammatory Bowel Diseases
Yang Tan, Xingxin Wu, Jing Sun, Wenjie Guo, Fangyuan Gong, Fenli Shao, Tao Tan, Yi Cao, Bingfeng Zheng, Yanhong Gu, Yang Sun, Qiang Xu
Interferon gamma (IFN-γ) signaling in T cells plays an important role in developing T helper 1 (Th1)-mediated inflammation. Selective regulation of IFN-γ signaling is an attractive strategy for treating Th1-mediated immune diseases. In this study, we aimed to explore possible means of targeting IFN-γ signaling by using small molecule compound. A synthetic small molecule FC9 was identified as it selectively inhibited IFN-γ signaling in T cells without suppressing interleukin 4 (IL-4) signaling. Furthermore, FC9 inhibited IFN-γ-induced Janus kinase 2 (JAK2) activation via competing with IFN-γ for binding to IFN-γ receptor 1 (IFN-γ R1)...
October 14, 2016: Biochemical Pharmacology
Xin Chen, Yingjie Nie, Haitao Xiao, Zhaoxiang Bian, Anthony J Scarzello, Na-Young Song, Anna L Trivett, De Yang, Joost J Oppenheim
No abstract text is available yet for this article.
October 13, 2016: Scientific Reports
Ernest H Law, Melissa Badowski, Yu-Ting Hung, Kimberly Weems, Angelica Sanchez, Todd A Lee
OBJECTIVE: Microscopic colitis (MC) is a chronic inflammatory disease of the colon that is characterized by chronic, watery, nonbloody diarrhea. Concern regarding a potential association between proton-pump inhibitors (PPIs) and MC has recently emerged. We sought to systematically review and summarize the evidence for the potential association between PPIs and MC. DATA SOURCES: We systematically searched EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, and Google Scholar using the terms proton-pump inhibitors (omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, or esomeprazole), microscopic colitis, collagenous colitis, and lymphocytic colitis STUDY SELECTION: Full-text, English-language reports of case reports/series, observational studies, experimental studies, and systematic reviews/meta-analyses published between January 2000 to August 2016 were included...
October 12, 2016: Annals of Pharmacotherapy
Adnan Hassan Tahir, Juan Wan, Manoj Kumar Shah, Habibullah Janyaro, Xiao-Jing Li, Ming-Xing Ding
BACKGROUND: Visceral hypersensitivity (VH) is a common condition in many gastrointestinal disorders such as inflammatory bowel diseases (IBDs) in human and animals. Most studies often induce Crohn's disease/colitis to investigate VH in small experimental animals. Although farm animals commonly suffer from IBDs, their VH has not been investigated so far. Because goats can suffer from Johne's disease, a naturally occurring Crohn's-like disease, they may be suitable to be used for studying the mechanism underlying VH in common intestinal disorders of large animals...
October 6, 2016: Acta Veterinaria Scandinavica
Yong-Ping Ding, Yannick Ladeiro, Ian Morilla, Yoram Bouhnik, Assiya Marah, Hatem Zaag, Dominique Cazals-Hatem, Philippe Seksik, Fanny Daniel, Jean-Pierre Hugot, Gilles Wainrib, Xavier Treton, Eric Ogier-Denis
BACKGROUNDS AND AIMS: The effect of cigarette smoking (CS) is ambivalent since smoking improves ulcerative colitis (UC) while it worsens Crohn's disease (CD). Although this clinical relationship between IBD and tobacco is well established, only a few experimental works have investigated the effect of smoking on the colonic barrier homeostasis focusing on xenobiotic detoxification genes. METHODS: A comprehensive and integrated comparative analysis of the global xenobiotic detoxification capacity of the normal colonic mucosa of healthy smokers (n=8) and non-smokers (n=9) versus the non-affected colonic mucosa of UC patients (n=19) was performed by qPCR...
October 4, 2016: Journal of Crohn's & Colitis
Yoshihiro Hirata, Sozaburo Ihara, Kazuhiko Koike
Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disorder that includes two distinct disease categories: ulcerative colitis and Crohn's disease. Epidemiological, genetic, and experimental studies have revealed many important aspects of IBD. Genetic susceptibility, inappropriate immune responses, environmental changes, and intestinal microbiota are all associated with the development of IBD. However, the exact mechanisms of the disease and the interactions among these pathogenic factors are largely unknown...
October 1, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Eun-Joo Jeon, Munkhtugs Davaatseren, Jin-Taek Hwang, Jae Ho Park, Haeng Jeon Hur, Ae Sin Lee, Mi Jeong Sung
In patients with inflammatory bowel disease (IBD), inflammation is induced and maintained by lymphangiogenesis and angiogenesis. 3,3'-Diindolylmethane (DIM) is a natural product formed in acidic conditions from indole-3-carbinol in cruciferous vegetables, and it is known for its chemotherapeutic activity. This study evaluated DIM's effects on angiogenesis, lymphangiogenesis, and inflammation in a mouse colitis model. Experimental colitis was induced in mice by administering 3% dextran sulfate sodium (DSS) via drinking water...
October 4, 2016: Journal of Agricultural and Food Chemistry
Krzysztof Siczek, Hubert Zatorski, Anna Chmielowiec-Korzeniowska, Jolanta Pulit-Prociak, Magdalena Śmiech, Radzisław Kordek, Leszek Tymczyna, Marcin Banach, Jakub Fichna
The aim of our study was to investigate the effect of newly developed silver nanoparticle aqueous suspensions NanoAg1 and NanoAg2 in the mouse models mimicking ulcerative colitis (UC) and Crohn's disease (CD). NanoAg1 and NanoAg2 were synthesized in aqueous medium with the involvement of tannic acid. To elucidate their anti-inflammatory activity, semi-chronic mouse models of inflammation induced by DSS addition to drinking water and intracolonic (i.c.) administration of TNBS were used. NanoAg1 and NanoAg2 (0...
October 3, 2016: Chemical Biology & Drug Design
C Preston Neff, Matthew E Rhodes, Kathleen L Arnolds, Colm B Collins, Jody Donnelly, Nichole Nusbacher, Paul Jedlicka, Jennifer M Schneider, Martin D McCarter, Michael Shaffer, Sarkis K Mazmanian, Brent E Palmer, Catherine A Lozupone
Zwitterionic capsular polysaccharides (ZPSs) are bacterial products that modulate T cells, including inducing anti-inflammatory IL-10-secreting T regulatory cells (Tregs). However, only a few diverse bacteria are known to modulate the host immune system via ZPS. We present a genomic screen for bacteria encoding ZPS molecules. We identify diverse host-associated bacteria, including commensals and pathogens with known anti-inflammatory properties, with the capacity to produce ZPSs. Human mononuclear cells stimulated with lysates from putative ZPS-producing bacteria induce significantly greater IL-10 production and higher proportions of Tregs than lysates from non-ZPS-encoding relatives or a commensal strain of Bacteroides cellulosilyticus in which a putative ZPS biosynthetic operon was genetically disrupted...
October 12, 2016: Cell Host & Microbe
Xiangyu Chen, Lingyun Li, Muhammad Noman Khan, Lifeng Shi, Zhongyan Wang, Fang Zheng, Feili Gong, Min Fang
In inflammatory bowel diseases (IBD), high mobility group box 1 (HMGB1), as an endogenous inflammatory molecule, can promote inflammatory cytokines secretion by acting on TLR2/4 resulting in tissue damage. The underlying mechanisms remain unclear. Here we report a novel role of HMGB1 in controlling the maintenance and function of intestine-resident group-3 innate lymphoid cells (ILC3s) that are important innate effector cells implicated in mucosal homeostasis and IBD pathogenesis. We showed that mice treated with anti-HMGB1 Ab, or genetically deficient for TLR2(-/-) or TLR4(-/-) mice, displayed reduced intestinal inflammation...
September 26, 2016: Innate Immunity
Jayson X Chen, Hong Wang, Anna Liu, Lanjing Zhang, Kenneth Reuhl, Chung S Yang
In the past decades, experimental rodent models developed to study the pathogenesis of human colorectal cancer (CRC) generally employed synthetic chemical carcinogens or genetic manipulation. Our lab, in order to establish a more physiologically relevant CRC model, recently developed a colon carcinogenesis model induced by the meat-derived dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and promoted by dextran sodium sulfate (DSS)-induced colitis in the cytochrome P450 1A-humanized (hCYP1A) mice...
September 23, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Amit Arya, Dipak K Majumdar, Dharam Pal Pathak, Anil K Sharma, Alok R Ray
Colon-targeted microparticles loaded with a model anti-inflammatory drug were fabricated using especially designed acrylic acid-butyl methacrylate copolymers. Microparticles were prepared by oil-in-oil solvent evaporation method using Span 80 as emulsifier. Microparticles were found to be spherical in shape, hemocompatible and anionic with zeta potential of -27.4 and -29.0 mV. Entrapment of drug in the microparticles was confirmed by Fourier transform infrared (FTIR) spectroscopy. However, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) revealed amorphous nature of microparticles due to the dilution effect of amorphous polymer...
October 6, 2016: Drug Development and Industrial Pharmacy
Reza Rahimian, Mohammad Reza Zirak, Mojtaba Keshavarz, Nahid Fakhraei, Ahmad Mohammadi-Farani, Hanan Hamdi, Kazem Mousavizadeh
Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal (GI) tract. Tropisetron, a selective 5-HT3 receptor antagonist, is highly used to counteract chemotherapy-induced emesis. Previous studies revealed the anti-inflammatory properties of this drug. The aim of this study was to evaluate the role of peroxisome proliferator-activated receptor gamma (PPARγ) receptor in the protective effect of tropisetron in an animal model of ulcerative colitis. Experimental colitis was induced by a single intra-colonic instillation of 4% (V/V) acetic acid in male rats...
September 20, 2016: Immunopharmacology and Immunotoxicology
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