Interleukin-8 gene regulation in intestinal epithelial cells infected with rotavirus:: Role of viral-induced IκB kinase activation
Interleukin-8 gene regulation in intestinal epithelial cells infected with rotavirus:: Role of viral-induced IκB kinase activation
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DOI：
10.1006/viro.2002.1475
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发表时间：
2002-06-20
期刊：
影响因子：
3.7
通讯作者：
Brasier, AR
中科院分区：
文献类型：
--
作者：
Casola, A;Garofalo, RP;Brasier, AR
轮状病毒是儿童腹泻的主要病原体，也是严重小儿胃肠炎的最常见原因。轮状病毒感染局限于排列在小肠绒毛上的成熟肠上皮细胞。肠上皮细胞在感染和细胞因子刺激下能够产生趋化因子，这是一个调节白细胞迁移和活化的小趋化细胞因子家族，我们先前已经表明，轮状病毒感染肠上皮细胞系HT-29诱导CXC趋化因子白细胞介素-（IL）8表达增加，在病毒感染期间负责肠上皮细胞中IL-8基因转录调控的机制尚未完全阐明。本研究旨在探讨轮状病毒感染HT-29细胞后IL-8基因表达的分子机制。瞬时转染分析IL-8启动子5'端缺失和突变驱动荧光素酶报告基因的表达表明，活化蛋白-（AP）1和核因子-（NF）kappaB元件是轮状病毒感染期间IL-8启动子激活所必需的。NF-κ B活化对IL-8基因表达的重要性进一步通过在阻断NF-κ B胞质抑制剂IkappaB-α的降解后抑制轮状病毒诱导的IL-8基因转录和蛋白质合成来证明，轮状病毒感染HT-29诱导的IkappaB激酶（IKK）激活和IKK-β显性失活突变体的过表达大大降低了轮状病毒诱导的IL-10表达。8启动子激活和NF-κ B驱动的转录，表明IKK参与轮状病毒诱导的IL-8基因表达和NF-κ B激活，（C）2002 Elsevier Science（USA）。
Rotavirus is the major etiologic agent of diarrhea in children and the most common cause of severe pediatric gastroenteritis, Rotavirus infection is limited to mature enterocytes that line the villi of the small intestine Gut epithelial Cells, upon infection and cytokine stimulation, are able to produce chemokines, a family of small chemotactic cytokines that regulate the migration and activation of leukocytes, We have previously shown that rotavirus infection of the intestinal epithelial cell line HT-29 induces increased expression of the CXC chemokine interleukin-(IL) 8, Mechanisms responsible for the transcriptional regulation of the IL-8 gene in intestinal epithelial cells during viral infections have not been fully elucidated Therefore, the purpose of this study was to define the molecular mechanisms of IL-8 gene expression in HT-29 cells infected with rotavirus. Transient transfection analysis of 5' deletions and mutations of the IL-8 promoter driving expression of luciferase reporter gene indicates that the activating protein-(AP) 1 and nuclear factor- (NF) kappaB elements are necessary for IL-8 promoter activation during rotavirus infection. The importance of NF-kappaB activation for IL-8 gene expression was further demonstrated by the inhibition of rotavirus-induced IL-8 gene transcription and protein synthesis following blockade of degradation of the NF-kappaB cytoplasmic inhibitor IkappaB-alpha, Rotavirus infection of HT-29-induced IkappaB kinase (IKK) activation and overexpression of a dominant negative mutant of IKK-beta greatly reduced rotavirus-induced IL-8 promoter activation and NF-kappaB-driven transcription, indicating that IKK is involved in rotavirus-induced IL-8 gene expression and NF-kappaB activation, (C) 2002 Elsevier Science (USA).