Differential alteration in intestinal epithelial cell expression of Toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease
Differential alteration in intestinal epithelial cell expression of Toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease
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DOI：
10.1128/iai.68.12.7010-7017.2000
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发表时间：
2000-12-01
影响因子：
3.1
通讯作者：
Podolsky, DK
中科院分区：
文献类型：
--
作者：
Cario, E;Podolsky, DK
炎症性肠病（IBD）中肠道炎症反应的启动和持续可能源于肠道上皮对内生的肠腔菌群的过度宿主防御反应。肠道上皮细胞系组成性表达几种有功能的Toll样受体（TLRs），它们似乎是先天反应系统的关键调节因子。本研究的目的是描述IBD患者原代肠道上皮细胞中TLR2、TLR3、TLR4和TLR5的表达模式。从IBD患者（克罗恩病[CD]、溃疡性结肠炎[UC]）和对照组收集小肠和结肠活检标本。使用针对TLR2、TLR3、TLR4和TLR5的多克隆抗体通过免疫荧光组织化学对非IBD标本进行评估。正常黏膜的原代肠道上皮细胞（IEC）组成性表达TLR3和TLR5，而TLR2和TLR4仅勉强可检测到。在活动性IBD中，肠道上皮中TLR3和TLR4的表达受到不同的调节。在活动性CD中，IEC中的TLR3显著下调，但在UC中没有。相反，在UC和CD中，TLR4均强烈上调。在IBD中，TLR2和TLR5的表达保持不变。这些数据表明，IBD可能与肠道上皮中选择性TLR表达的独特变化有关，这意味着先天反应系统的改变可能有助于这些疾病的发病机制。
Initiation and perpetuation of the inflammatory intestinal responses in inflammatory bowel disease (IBD) may result from an exaggerated host defense reaction of the intestinal epithelium to endogenous lumenal bacterial flora. Intestinal epithelial cell lines constitutively express several functional Toll like receptors (TLRs) which appear to be key regulators of the innate response system. The aim of this study was to characterize the expression pattern of TLR2, TLR3, TLR4, and TLR5 in primary intestinal epithelial cells from patients with IBD. Small intestinal and colonic biopsy specimens were collected from patients with IBD (Crohn's disease [CD], ulcerative colitis [UC]) and controls. Non-IBD specimens were assessed by immunofluorescence histochemistry using polyclonal antibodies specific for TLR2, TLR3, TLR4, and TLR5. Primary intestinal epithelial cells (IEC) of normal mucosa constitutively expressed TLR3 and TLR5, while TLR2 and TLR4 were only barely detectable. In active IBD, the expression of TLR3 and TLRL4 was differentially modulated in the intestinal epithelium. TLR3 was significantly downregulated in IEC in active CD but not in UC. In contrast, TLR4 was strongly upregulated in both UC and CD. TLR2 and TLR5 expression remained unchanged in IBD. These data suggest that IBD may be associated with distinctive changes in selective TLR expression in the intestinal epithelium, implying that alterations in the innate response system may contribute to the pathogenesis of these disorders.