Zhu Z, Tang W, Ray A, Wu Y, Einarsson O, Landry M L, Gwaltney J, Elias J A
Yale University School of Medicine, Department of Internal Medicine, New Haven, Connecticut 06520-8057, USA.
J Clin Invest. 1996 Jan 15;97(2):421-30. doi: 10.1172/JCI118431.
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.
为了进一步了解鼻病毒（RV）的生物学特性，我们确定了RV感染期间是否会产生白细胞介素-6（IL-6），并对RV刺激肺细胞产生IL-6的机制进行了表征。与正常人和症状轻微的志愿者不同，RV攻击后患上感冒的患者的鼻腔冲洗液中检测到了IL-6。RV14和RV1A分别是主要和次要受体组的RV，在体外是IL-6蛋白产生的有效刺激物。这些作用与IL-6 mRNA积累和基因转录的显著增加有关。RV也是IL-6启动子驱动的荧光素酶活性的有效刺激物。通过核因子（NF）-IL-6位点的突变，这种刺激作用略有降低，而通过该启动子中NF-κB位点的突变则被消除。由p65、p50和p52 NF-κB部分介导的NF-κB-DNA结合活性在RV感染的细胞中迅速被诱导。激活蛋白1-DNA结合没有类似的改变。这些研究表明，在有症状的RV感染期间会产生IL-6，RV是IL-6分泌的有效刺激物，并且RV刺激IL-6的产生是由NF-κB依赖性转录刺激途径介导的。IL-6可能在RV感染的发病机制中起重要作用，而NF-κB激活可能是RV诱导的病理过程中的一个重要事件。
