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Colitis mice

Anna L Means, Tanner J Freeman, Jing Zhu, Luke G Woodbury, Paula Marincola-Smith, Chao Wu, Anne R Meyer, Connie J Weaver, Chandrasekhar Padmanabhan, Hanbing An, Jinghuan Zi, Bronson C Wessinger, Rupesh Chaturvedi, Tasia D Brown, Natasha G Deane, Robert J Coffey, Keith T Wilson, J Joshua Smith, Charles L Sawyers, James R Goldenring, Sergey V Novitskiy, M Kay Washington, Chanjuan Shi, R Daniel Beauchamp
Background & Aims: Chronic inflammation is a predisposing condition for colorectal cancer. Many studies to date have focused on proinflammatory signaling pathways in the colon. Understanding the mechanisms that suppress inflammation, particularly in epithelial cells, is critical for developing therapeutic interventions. Here, we explored the roles of transforming growth factor β (TGFβ) family signaling through SMAD4 in colonic epithelial cells. Methods: The Smad4 gene was deleted specifically in adult murine intestinal epithelium...
2018: Cellular and Molecular Gastroenterology and Hepatology
Vincent W Yang, Yang Liu, Julie Kim, Kenneth R Shroyer, Agnieszka B Bialkowska
Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, regulates homeostasis of the intestinal epithelium. Previously, it was reported that KLF4 functions as a tumor suppressor in colorectal cancer. Here, evidence demonstrates that KLF4 mitigates the development and progression of colitis-associated colorectal cancer (CAC) in a murine model. Mice with intestinal epithelium-specific deletion of Klf4 (Klf4DIS) and control mice (Klf4fl/fl) were used to explore the role of KLF4 in the development of azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced CAC...
August 14, 2018: Molecular Cancer Research: MCR
Yan Zhou, Hanyang Liu, Jun Song, Liang Cao, Liming Tang, Chunjian Qi
Sinomenine (SIN), a pure alkaloid isolated from Sinomenium acutum, has been widely used in arthritis for its anti‑inflammatory effect, but little is known about the effect of SIN on human ulcerative colitis (UC). In the present study, the effect and mechanism of SIN was examined in a dextran sulfate sodium (DSS)‑induced murine colitis model, which mimics human UC. Oral administration of SIN significantly suppressed the elevated disease activity index and ameliorated colonic histological damage in a DSS‑induced colitis model...
August 10, 2018: Molecular Medicine Reports
Hisaya K Ono, Sayuri Yoshimura, Shouhei Hirose, Kouji Narita, Makoto Tsuboi, Krisana Asano, Akio Nakane
Proteoglycan (PG) is a complex glycohydrate, which is widely distributed in the extracellular matrix. It has been reported that daily oral administration of PG (extracted from salmon nasal cartilage) modulates the severity of proinflammatory cytokine responses in mouse experimental colitis, autoimmune encephalomyelitis, collagen‑induced arthritis and obesity‑induced inflammation. The present study investigated the effect of salmon nasal cartilage PG on allergic responses using a mouse model of papain‑induced respiratory inflammation...
August 8, 2018: Molecular Medicine Reports
Jingyun Xu, Lijia Wu, Pengcheng Yu, Mingxu Liu, Yixin Lu
Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease (CD), is a chronic autoimmune disease. Parasitic infections and their products have been shown protective effects on autoimmune diseases, including IBD. In this experiment, 96 male BALB/c mice aged 6-8 weeks were randomly divided into two large groups: prevention group and therapy group. The changes on the various indicators of colitis were detected to demonstrate that T. spiralis serine protease inhibitors can relieve the inflammatory severity of TNBS-induced colitis and to explore possible immunological mechanisms...
August 13, 2018: Clinical and Experimental Immunology
Guo Chao Niu, Lei Liu, Libo Zheng, Hong Zhang, David Q Shih, Xiaolan Zhang
BACKGROUND: A variety of extra-intestinal manifestations (EIMs), including hepatobiliary complications, are associated with inflammatory bowel disease (IBD). Mesenchymal stem cells (MSCs) have been shown to play a potential role in the therapy of IBD. This study was designed to investigate the effect and mechanism of MSCs on chronic colitis-associated hepatobiliary complications using mouse chronic colitis models induced by dextran sulfate sodium (DSS). METHODS: DSS-induced mouse chronic colitis models were established and treated with MSCs...
August 13, 2018: BMC Gastroenterology
Simon Ghaly, Nadeem O Kaakoush, Frances Lloyd, Lavinia Gordon, Cynthia Forest, Ian C Lawrance, Prue H Hart
Reduced sunlight exposure has been associated with an increased incidence of Crohn's disease and ulcerative colitis. The effect of ultraviolet radiation (UVR) on the faecal microbiome and susceptibility to colitis has not been explored. C57Bl/6 female mice were fed three different vitamin D-containing diets for 24 days before half of the mice in each group were UV-irradiated (1 kJ/m²) for each of four days, followed by twice-weekly irradiation of shaved dorsal skin for 35 days. Faecal DNA was extracted and high-throughput sequencing of the 16S RNA gene performed...
August 11, 2018: Nutrients
Aravind Shekar, Shylaja Ramlal, Joseph Kingston Jeyabalaji, Murali Harishchandra Sripathy
Ruminants are the major reservoirs of Escherichia coli O157:H7 and its fecal shedding mainly act as a source of entry of this pathogen into the human food chain. In humans, E. coli O157:H7 infection causes diarrhea, hemorrhagic colitis and hemolytic uremic syndrome. Intimate adherence of E. coli O157:H7 is mediated by Translocated intimin receptor (Tir) to which intimin binds in the host cell. Since E. coli O157:H7 colonizes intestinal epithelium, the mucosal vaccine has a potential to prevent its colonization...
August 10, 2018: International Immunopharmacology
Goran Tomic, Edward Morrissey, Sarah Kozar, Shani Ben-Moshe, Alice Hoyle, Roberta Azzarelli, Richard Kemp, Chandra Sekhar Reddy Chilamakuri, Shalev Itzkovitz, Anna Philpott, Douglas J Winton
The intestinal epithelium is largely maintained by self-renewing stem cells but with apparently committed progenitors also contributing, particularly following tissue damage. However, the mechanism of, and requirement for, progenitor plasticity in mediating pathological response remain unknown. Here we show that phosphorylation of the transcription factor Atoh1 is required for both the contribution of secretory progenitors to the stem cell pool and for a robust regenerative response. As confirmed by lineage tracing, Atoh1+ cells (Atoh1(WT)CreERT2 mice) give rise to multilineage intestinal clones both in the steady state and after tissue damage...
July 27, 2018: Cell Stem Cell
Kai Zhou, Rui Cheng, Bei Liu, Lei Wang, Haifeng Xie, Chaofeng Zhang
BACKGROUND: Despite the higher morbidity of ulcerative colitis (UC), available treatments remain unsatisfactory in recent years. A natural flavone eupatilin (Eup) is known to inhibit the intestinal contraction. PURPOSE: The protective role of Eup in intestinal inflammation remains unclear. This study attempted to determine the bioactivity of Eup against colitis and clarify the mechanism of action. STUDY DESIGN: The in vitro effects of Eup on lipopolysaccharide-induced human THP-M macrophage activation and tumour necrosis factor-α (TNF-α)-damaged intestinal epithelial (NCM460) cells were explored to clarify its potential protective effects...
July 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Chunwei Cheng, Jun Tan, Wei Qian, Lei Zhang, Xiaohua Hou
AIMS: Gut inflammation has been put forward to be associated with hepatic injury in the clinical practice. The dismantled intestinal barrier was highly concerned, however, largely unknown about the role of gut-vascular barrier (GVB) in this process. This study aimed to investigate if inflamed gut directly contributes to the progression of non-alcoholic steatohepatitis (NASH), especially attention to the GVB dysfunction. MAIN METHODS: Male C57bl/6 mice were fed with a high-fat diet (HFD) and 1% DSS for 12 weeks...
August 7, 2018: Life Sciences
Pekka Määttänen, Eberhard Lurz, Steven R Botts, Richard Y Wu, Chiu William Yeung, Bo Li, Sumayyah Abiff, Kathene C Johnson-Henry, Dion Lepp, Krista A Power, Agostino Pierro, Marc E Surette, Philip M Sherman
Flaxseed is high in omega-3 polyunsaturated fatty acids, fiber and lignans known to lower cholesterol levels. However, its use for prevention or treatment of inflammatory bowel diseases has yielded mixed results, perhaps related to dietary interactions. In this study, we evaluated the impact of ground flaxseed supplementation on the severity of Citrobacter rodentium-induced colitis in the setting of either a high fat (HF; ~36 %kcal) or reduced fat (RF; ~12 %kcal) diet. After weaning, C57BL/6 mice (n=8-15/treatment) were fed ground flaxseed (7g/100g diet) with either HF (HF Flx) or RF (RF Flx) diets for four weeks prior to infection with C...
August 10, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Tadafumi Fukata, Tsunekazu Mizushima, Junichi Nishimura, Daisuke Okuzaki, Xin Wu, Haruka Hirose, Yuhki Yokoyama, Yui Kubota, Kazuya Nagata, Naoto Tsujimura, Akira Inoue, Norikatsu Miyoshi, Naotsugu Haraguchi, Hidekazu Takahashi, Taishi Hata, Chu Matsuda, Hisako Kayama, Kiyoshi Takeda, Yuichiro Doki, Masaki Mori, Hirofumi Yamamoto
The incidence of inflammatory bowel disease (IBD) is increasing. Nucleic acid-based medicine has potential as a next-generation treatment, but it is rarely successful with IBD. The aim of this study was to establish a microRNA-based therapy in an IBD model. For this purpose, we used microRNA-29 (miR-29) and a supercarbonate apatite (sCA) nanoparticle as a drug delivery system. Injection of sCA-miR-29a-3p or sCA-miR-29b-3p into mouse tail veins markedly prevented and restored inflammation because of dextran sulfate sodium (DSS)-induced colitis...
August 6, 2018: Molecular Therapy. Nucleic Acids
Ping Zhang, Ying Chen, Tao Zhang, Jiang Zhu, Lei Zhao, Jianshuang Li, Guangzhi Wang, Yongchun Li, Shuchang Xu, Ake Nilsson, Rui-Dong Duan
Intestinal alkaline sphingomyelinase (alk-SMase) cleaves phosphocholine from sphingomyelin, platelet-activating factor (PAF), and lysophosphatidylcholine. We recently found that colitis-associated colon cancer was 4-5 fold enhanced in alk-SMase knockout mice. Here we further studied pathogenesis of colitis induced by dextran sulfate sodium (DSS) in wild type (WT) and the knockout mice. Comparing with WT mice, knockout mice demonstrated greater body weight loss, more severe bloody diarrhea, broader inflammatory cell infiltration, and more serious epithelial injury...
August 7, 2018: Journal of Lipid Research
Colm B Collins, Pamela R Puthoor, Tom T Nguyen, Paul Jedlicka, Jacob E Friedman, Edwin F de Zoeten
Background and Aims: Inflammatory Bowel Diseases (IBD) are chronic intestinal inflammatory conditions in part mediated by CD4+ T cells. Anti-inflammatory Foxp3+ regulatory T cells (Treg) maintain immune homeostasis and protect against IBD development via multiple mechanisms including cytokine secretion and cell-cell interaction. CCAAT enhancer binding protein-beta (C/EBPβ) is a stress-responsive transcription factor linked with IBD susceptibility. Whole-body C/EBPβ deficiency induces CD4+ T cell-predominant hyperproliferation and we hypothesize that this may be due to impaired Treg function...
July 31, 2018: Journal of Crohn's & Colitis
Bruna Girardi, Mariabeatrice Principi, Maria Pricci, Floriana Giorgio, Andrea Iannone, Giuseppe Losurdo, Enzo Ierardi, Alfredo Di Leo, Michele Barone
Based on preliminary "in vitro" experience, we assessed whether an enriched nutritional formulation with estrogen receptor (ER)-beta agonist and anti-inflammatory properties may prevent inflammation-associated colorectal cancer (CRC) in an animal model.Study sample enclosed 110 C57BL/6J male mice. Forty underwent dietary supplement safety assessment (20 standard and 20 enriched formulation). Seventy were treated with azoxymethane (AOM)/dextran-sulfate-sodium (DSS) and divided into two groups: 35 received standard and 35 the enriched formulation (curcumin, boswellic acids, silymarin and maltodextrins)...
August 6, 2018: Carcinogenesis
Jing Ren, Liang Ding, Dongya Zhang, Guoping Shi, Qianyun Xu, Sunan Shen, Yaping Wang, Tingting Wang, Yayi Hou
Long non-coding RNAs (lncRNAs) are involved in the pathology of various tumors, including colorectal cancer (CRC). The crosstalk between carcinoma- associated fibroblasts (CAFs) and cancer cells in the tumor microenvironment promotes tumor development and confers chemoresistance. In this study, we further investigated the underlying tumor-promoting roles of CAFs and the molecular mediators involved in these processes. Methods: The AOM/DSS-induced colitis-associated cancer (CAC) mouse model was established, and RNA sequencing was performed...
2018: Theranostics
Stefano Bruscoli, Daniele Sorcini, Sara Flamini, Andrea Gagliardi, Francesco Adamo, Simona Ronchetti, Graziella Migliorati, Oxana Bereshchenko, Carlo Riccardi
Glucocorticoid-induced leucine zipper (GILZ) is transcriptionally upregulated by glucocorticoids (GCs) and mediates many of the anti-inflammatory effects of GCs. Since B cell activity has been linked to cytokine production and modulation of inflammatory responses, we herein investigated the role of GILZ in B cells during colitis development. B cell-specific gilz knock-out (gilz B cKO) mice exhibited increased production of the pro-inflammatory cytokine IFN-γ in B cells, and consequently CD4+ T cell activation...
2018: Frontiers in Immunology
Xiaojun Lin, Qiuyi Sun, Ling Zhou, Minhong He, Xiaoying Dong, Mingqiang Lai, Miao Liu, Yongchun Su, Chunhong Jia, Zelong Han, Side Liu, Hang Zheng, Yu Jiang, Hui Ling, Mangmang Li, Juan Chen, Zhipeng Zou, Xiaochun Bai
The functional role of colonic epithelium in the pathogenesis of ulcerative colitis (UC) remains unclear. Here, we reveal a novel mechanism by which colonic epithelia recruit T helper-17 (Th17) cells during the onset of UC. mTOR complex 1 (mTORC1) was hyper-activated in colonic epithelia of UC mice. While colonic epithelial TSC1 (mTORC1 negative regulator) disruption induced constitutive mTORC1 activation in the colon epithelia and aggravated UC, RPTOR (essential mTORC1 component) depletion inactivated mTORC1 and ameliorated UC...
August 6, 2018: Mucosal Immunology
J Garrido-Mesa, F Algieri, A Rodríguez-Nogales, T Vezza, M P Utrilla, F Garcia, N Chueca, M E Rodriguez-Cabezas, N Garrido-Mesa, J Gálvez
OBJECTIVE: The use of immunomodulatory antibiotics to simultaneously target different factors involved in intestinal inflammatory conditions is an interesting but understudied pharmacological strategy. A great therapeutic potential has been obtained with minocycline and doxycycline in experimental colitis. Therefore, understanding the contribution of the different activities of immunomodulatory tetracyclines is crucial for the improvement and translation of their use into clinic. Design A comparative pharmacological study including tetracyclines and other antibiotic or immunomodulatory drugs was performed in 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice...
August 1, 2018: Biochemical Pharmacology
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