Changes in colon gene expression associated with increased colon inflammation in interleukin-10 gene-deficient mice inoculated with Enterococcus species.
Changes in colon gene expression associated with increased colon inflammation in interleukin-10 gene-deficient mice inoculated with Enterococcus species.
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DOI：
10.1186/1471-2172-11-39
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发表时间：
2010-07-15
期刊：
影响因子：
3
通讯作者：
Roy NC
中科院分区：
文献类型：
--
作者：
Barnett MP;McNabb WC;Cookson AL;Zhu S;Davy M;Knoch B;Nones K;Hodgkinson AJ;Roy NC
对正常肠道细菌的不适当反应可能参与炎症性肠病(IBD，如克罗恩病(CD)、溃疡性结肠炎(UC))的发生，宿主基因组的变异可能参与这一过程。IL-10基因缺陷(IL10-/-)小鼠主要在结肠发生类CD结肠炎，部分原因是对包括肠球菌在内的正常肠道细菌的不适当反应，因此被用作CD的动物模型。最近报道了在IL10-/-小鼠模型中与炎症相关的盲肠基因表达水平变化的全面特征。我们的目的是研究口服细菌接种12株从小牛或家禽分离的粪肠球菌(EF)、从健康对照小鼠采集的复合肠道菌群(CIF)或两者的混合物(EF·CIF)后，Il10-/-和C57BL/6J(C57；对照)小鼠结肠基因表达水平的变化。我们研究了两个假设：(1)口服接种Il10-/-小鼠会导致比没有接受接种的Il10-/-小鼠更严重和更一致的肠道炎症，(2)这种炎症与结肠基因表达水平的变化有关，类似于以前在人类研究中观察到的变化，因此这些小鼠将是研究人类CD的合适模型。12周龄时，将从完整结肠提取的总RNA与Agilent 44k小鼠阵列杂交。使用用于微阵列分析的线性模型(BioConductor)鉴定差异表达的基因，并使用GeneSpring GX和Invenity Path分析软件对这些基因进行聚类。IL10-/-小鼠接种后肠道炎症反应加重，其中EF和EF·CIF组的作用最强。Il10-/-小鼠接种EF或EF·CIF后差异表达的基因与炎症(111个差异表达基因)、免疫应答(209个基因)、抗原提呈(11个基因，特别是主要组织相容性复合体II类)、脂肪酸代谢(30个基因)和解毒(31个基因)有关。我们的结果表明，接种含有肠球菌的溶液的Il10-/-小鼠的结肠炎与类似于人IBD，尤其是CD的基因表达变化有关，特别是对于EF·CIF接种，这是研究与人类CD相关的食物-基因相互作用的合适模型。
Inappropriate responses to normal intestinal bacteria may be involved in the development of Inflammatory Bowel Diseases (IBD, e.g. Crohn's Disease (CD), Ulcerative Colitis (UC)) and variations in the host genome may mediate this process. IL-10 gene-deficient (Il10-/-) mice develop CD-like colitis mainly in the colon, in part due to inappropriate responses to normal intestinal bacteria including Enterococcus strains, and have therefore been used as an animal model of CD. Comprehensive characterization of changes in cecum gene expression levels associated with inflammation in the Il10-/- mouse model has recently been reported. Our aim was to characterize changes in colonic gene expression levels in Il10-/- and C57BL/6J (C57; control) mice resulting from oral bacterial inoculation with 12 Enterococcus faecalis and faecium (EF) strains isolated from calves or poultry, complex intestinal flora (CIF) collected from healthy control mice, or a mixture of the two (EF·CIF). We investigated two hypotheses: (1) that oral inoculation of Il10-/- mice would result in greater and more consistent intestinal inflammation than that observed in Il10-/- mice not receiving this inoculation, and (2) that this inflammation would be associated with changes in colon gene expression levels similar to those previously observed in human studies, and these mice would therefore be an appropriate model for human CD. At 12 weeks of age, total RNA extracted from intact colon was hybridized to Agilent 44 k mouse arrays. Differentially expressed genes were identified using linear models for microarray analysis (Bioconductor), and these genes were clustered using GeneSpring GX and Ingenuity Pathways Analysis software. Intestinal inflammation was increased in Il10-/- mice as a result of inoculation, with the strongest effect being in the EF and EF·CIF groups. Genes differentially expressed in Il10-/- mice as a result of EF or EF·CIF inoculation were associated with the following pathways: inflammatory disease (111 genes differentially expressed), immune response (209 genes), antigen presentation (11 genes, particularly major histocompatability complex Class II), fatty acid metabolism (30 genes) and detoxification (31 genes). Our results suggest that colonic inflammation in Il10-/- mice inoculated with solutions containing Enterococcus strains is associated with gene expression changes similar to those of human IBD, specifically CD, and that with the EF·CIF inoculum in particular this is an appropriate model to investigate food-gene interactions relevant to human CD.
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影响因子：
64.8
作者：
Brandl, Katharina;Plitas, George;Mihu, Coralia N.;Ubeda, Carles;Jia, Ting;Fleisher, Martin;Schnabl, Bernd;DeMatteo, Ronald P.;Pamer, Eric G.
通讯作者：
Pamer, Eric G.
影响因子：
6
作者：
Balish, E;Warner, T
通讯作者：
Warner, T
影响因子：
1.9
作者：
Klein, W;Tromm, A;Epplen, JT
通讯作者：
Epplen, JT
影响因子：
5
作者：
Klein, W;Tromm, A;Epplen, JT
通讯作者：
Epplen, JT
影响因子：
4.9
作者：
Glas, J;Török, HP;Folwaczny, C
通讯作者：
Folwaczny, C