Selective Downregulation of Retinoic Acid-Inducible Gene I Within the Intestinal Epithelial Compartment in Crohn's Disease

Selective Downregulation of Retinoic Acid-Inducible Gene I Within the Intestinal Epithelial Compartment in Crohn's Disease
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DOI:
10.1002/ibd.21572
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发表时间:
2011-09-01
影响因子:
4.9
通讯作者:
Autschbach, Frank
Autschbach, Frank
中科院分区:
医学2区
文献类型:
--
作者:
Funke, Benjamin;Lasitschka, Felix;Autschbach, Frank

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背景:先天性免疫应答缺陷可能是克罗恩病(CD)和溃疡性结肠炎(UC)的发病机制之一。采用全局基因表达分析,这项研究的目的是确定特异性调控的基因在上皮细胞内的炎症性bowel disease(IBD)。方法:人回肠粘膜上皮部分的手术标本,通过激光显微切割。通过全局表达谱分析检测基因表达(n = 18,Affyflux)、定量逆转录聚合酶链反应(RT-PCR)(n = 35)、免疫印迹分析(n = 9)和免疫组织化学(n = 25)。全局表达谱显示,视黄酸诱导基因I(RIG-I)CD患者回肠上皮层内,但UC患者无。通过定量RT-PCR,免疫印迹分析和免疫组化证实下调RIG-I,一个已知的模式识别受体的病毒成分,可能有助于改变固有粘膜免疫反应,特别是在CD上皮下调。
Background: A defective innate immune response may contribute to the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC). Employing a global gene expression analysis, this study was aimed at identifying specifically regulated genes within the epithelial compartment in inflammatory bowel disease (IBD).Methods: The epithelial fraction of human ileal mucosa samples from surgical specimens was obtained by laser microdissection. Gene expression was examined by global expression profiling (n = 18, Affymetrix), quantitative reverse-transcription polymerase chain reaction (RT-PCR) (n = 35), immunoblot analysis (n = 9), and immunohistochemistry (n = 25).Results: Global expression profiling revealed a pronounced downregulation of the retinoic acid-inducible gene I (RIG-I) within the epithelial layer of the ileum in patients with CD but not with UC. The downregulation of RIG-I was confirmed by quantitative RT-PCR, immunoblot analysis, and immunohistochemistry.Conclusions: Epithelial downregulation of RIG-I, a known pattern recognition receptor for viral components, might contribute to alterations of the innate mucosal immune response, particularly in CD.