Molecular mechanisms for enhancement of human cytomegalovirus replication by chemokine, interleukin 8

趋化因子白介素 8 增强人巨细胞病毒复制的分子机制

• 批准号: 07670353
• 负责人: MURAYAMA Tsugiya
• 金额: $ 1.54万
• 依托单位: Kanazawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670353/
• 关键词: Cytomegalovirus; Interleukin 8; THP-1; AP-1; NF-kB; Northern blot; ノーザンブロット; IL-8レセプター

The association of CMV with IL-8, a chemotactic cytokine, has been suggested by several observations. We examined the effects of CMV on the production of IL-8 and also analyzed the molecular mechanisms of CMV-induced IL-8 production using THP-1 cells. THP-1 cells were infected with CMV,Towne strain. The production of IL-8 was measured by an ELISA.IL-8 specific transcript was detected by Northern blot. The transcriptional regulatory gene expression of IL-8 gene in response to CMV infection was measured by luciferase reporter gene assay. The nuclear factors which bind to the enhancer regions were also examined by electrophoretic mobility shift assay (EMSA). Infection with CMV induced IL-8 gene transcription in THP-1 cells, leading to IL-8 secretion. The functional analysis on the IL-8 gene revealed that both AP-1 and NF-kB factor binding elements were involved in conferring the responsiveness to CMV.Moreover, EMSA demonstrated that CMV induced the formation of NF-kB and AP-1 complexes. This study suggests that CMV modulates inflammatory responses associated with IL-8 production through activation of transcription factors.

几项观察表明，巨细胞病毒与趋化细胞因子IL-8有关。我们检测了CMV对IL-8产生的影响，并分析了CMV诱导THP-1细胞产生IL-8的分子机制。用巨细胞病毒Towne株感染THP-1细胞。用ELISA法检测IL-8的产生，Northern印迹法检测IL-8的特异性转录本。用荧光素酶报告基因检测IL-8基因转录调控基因在CMV感染过程中的表达。用凝胶迁移率改变分析(EMSA)检测与增强子区域结合的核因子。CMV感染诱导THP-1细胞IL-8基因转录，导致IL-8分泌。对IL-8基因的功能分析表明，AP-1和NF-kB因子结合元件都参与了对CMV的应答，EMSA还证实了CMV诱导了NF-kB和AP-1复合体的形成。这项研究表明，CMV通过激活转录因子来调节与IL-8产生相关的炎症反应。

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