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Ex vivo response to mucosal bacteria and muramyl dipeptide in inflammatory bowel disease

Ex vivo response to mucosal bacteria and muramyl dipeptide in inflammatory bowel disease

作     者:Claudia Loganes Erica Valencic Alessia Pin Elisa Marini Stefano Martelossi Samuele Naviglio Luigina De Leo Tarcisio Not Lorenzo Monasta Alberto Tommasini Annalisa Marcuzzi 

作者机构:Department of Medicine Surgery and Health Sciences University of Trieste Strada di Fiume Institute for Maternal and Child Health - IRCCS "Burlo Garofolo" 

出 版 物:《World Journal of Gastroenterology》 (世界胃肠病学杂志(英文版))

年 卷 期:2016年第22卷第44期

页      面:9734-9743页

核心收录:

学科分类:1002[医学-临床医学] 100201[医学-内科学(含:心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基  金:Supported by Institute for Maternal and Child Health-IRCCS"Burlo Garofolo" No.RC 03/09 

主  题:Gut-microbiota Crohn’s disease Ulcerative colitis Cytokines Inflammation 

摘      要:AIM To evaluate how mucosal bacteria impact on the spontaneous and muramyl dipeptide(MDP)-induced inflammation in Crohn s disease(CD) and ulcerative colitis(UC).METHODS Colonic mucosal biopsies were collected from children with active or remissive CD, UC and controls. Two tissue samples were taken from inflamed mucosal segments(in patients with active disease) or from noninflamed mucosa [in patients in remission or in healthy controls(HC)]. Experiments were performed in the presence or absence of antibiotics, to assess whether the disease-associated microbiota can modulate the cytokine response ex vivo. For this purpose, each specimen was half-cut to compare spontaneous and MDP-induced inflammation in the presence of live bacteria(LB) or antibiotics. After 24 h of culture, an array of 17 cytokines was assessed in supernatants. Statistical analyses were performed to find significant differences in single cytokines or in patterns of cytokine response in the different groups. RESULTS We demonstrated that subjects with CD display a spontaneous production of inflammatory cytokines including granulocyte-colony stimulating factor(G-CSF), interleukin(IL) 6, IL8, IL10 and IL12, that was not significantly influenced by the addition of antibiotics. UC specimens also displayed a trend of increased spontaneous secretion of several cytokines, which however was not significant due to broader variability among patients. After the addition of antibiotics, spontaneous IL8 secretion was significantly higher in UC than in controls. In HC, a trend towards the weakening of spontaneous IL8 production was observed in the presence of live mucosal bacteria with respect to the presence of antibiotics. In contrast, in the presence of LB UC showed an increasing trend of spontaneous IL8 production, while MDP stimulation resulted in lower IL8 production in the presence of antibiotics. We also showed that subjects with CD seem to have a lowered production of IL8 in response to MDP in the presence

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