Rhinovirus stimulation of interleukin-6 in vivo and in vitro. Evidence for nuclear factor kappa B-dependent transcriptional activation.
Rhinovirus stimulation of interleukin-6 in vivo and in vitro. Evidence for nuclear factor kappa B-dependent transcriptional activation.
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DOI：
10.1172/jci118431
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发表时间：
1996-01
期刊：
影响因子：
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通讯作者：
Zhou Zhu;Weiliang Tang;A. Ray;Yang Wu;O. Einarsson;M. Landry;J. Gwaltney;J. Elias
中科院分区：
文献类型：
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作者：
Zhou Zhu;Weiliang Tang;A. Ray;Yang Wu;O. Einarsson;M. Landry;J. Gwaltney;J. Elias
为了进一步了解鼻病毒 (RV) 的生物学特性，我们确定了 RV 感染期间是否产生 IL-6，并表征了 RV 刺激肺细胞产生 IL-6 的机制。与正常人和症状轻微的志愿者相比，在 RV 攻击后出现感冒的患者的鼻腔冲洗液中检测到了 IL-6。 RV14 和 RV1A，主要和次要受体组 RV，分别是体外 IL-6 蛋白产生的有效刺激剂。这些效应与 IL-6 mRNA 积累和基因转录的显着增加有关。 RV 也是 IL-6 启动子驱动的荧光素酶活性的有效刺激剂。这种刺激因核因子 (NF)-IL-6 位点的突变而适度减弱，并因该启动子中 NF-κ B 位点的突变而消除。由 p65、p50 和 p52 NF-kappa B 部分介导的 NF-kappa B-DNA 结合活性在 RV 感染的细胞中迅速诱导。激活蛋白 1-DNA 结合没有类似的改变。这些研究表明，IL-6 是在有症状的 RV 感染期间产生的，RV 是 IL-6 精化的有效刺激剂，并且 RV 刺激 IL-6 的产生是由 NF-κ B 依赖性转录刺激途径介导的。 IL-6 可能在 RV 感染的发病机制中发挥重要作用，并且 NF-κ B 激活可能是 RV 诱导的病理学中的重要事件。
To further understand the biology of rhinovirus (RV), we determined whether IL-6 was produced during RV infections and characterized the mechanism by which RV stimulates lung cell IL-6 production. In contrast to normals and minimally symptomatic volunteers, IL-6 was detected in the nasal washings from patients who developed colds after RV challenge. RV14 and RV1A, major and minor receptor group RVs, respectively, were potent stimulators of IL-6 protein production in vitro. These effects were associated with significant increases in IL-6 mRNA accumulation and gene transcription. RV was also a potent stimulator of IL-6 promoter-driven luciferase activity. This stimulation was modestly decreased by mutation of the nuclear factor (NF)-IL-6 site and abrogated by mutation of the NF-kappa B site in this promoter. An NF-kappa B-DNA binding activity, mediated by p65, p50, and p52 NF-kappa B moieties, was rapidly induced in RV-infected cells. Activator protein 1-DNA binding was not similarly altered. These studies demonstrate that IL-6 is produced during symptomatic RV infections, that RVs are potent stimulators of IL-6 elaboration, and that RV stimulation IL-6 production is mediated by an NF-kappa B-dependent transcriptional stimulation pathway. IL-6 may play an important role in the pathogenesis of RV infection, and NF-kappa B activation is likely to be an important event in RV-induced pathologies.