hCMV induced IL-6 release in trophoblast and trophoblast like cells

hCMV induced IL-6 release in trophoblast and trophoblast like cells
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DOI:
10.1016/j.jcv.2006.06.006
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发表时间:
2006-10-01
影响因子:
8.8
通讯作者:
Sinzger, Christian
Sinzger, Christian
中科院分区:
医学3区
文献类型:
--
作者:
Halwachs-Baumann, Gabriele;Weihrauch, Gisela;Sinzger, Christian

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背景:人巨细胞病毒(HCMV)感染滋养层细胞是母婴传播的重要事件,是母婴宫内感染的致病因素之一。滋养层细胞内病毒复制的不同取决于妊娠时间和滋养层细胞分化程度,可能影响这种传播。此外,滋养层细胞对巨细胞病毒感染的免疫反应也可能是重要的防御机制。目的:研究人巨细胞病毒在滋养层细胞和滋养层细胞样细胞(绒毛膜癌细胞)中的复制和IL-6的释放。研究设计:分离足月和早孕胎盘滋养层细胞,感染人巨细胞病毒。检测感染细胞上清液中HCMV的产生和释放,以及IL-6的释放和IL-6mRNA的产生。绒毛膜癌细胞株(JEG-3、JAR)同样处理。以未感染的滋养层细胞作为对照。结果:早孕滋养层细胞、足月滋养层细胞和JEG-3细胞中均可观察到HCMV的复制,但复制的动力学和效率不同。在JAR中没有观察到完整的病毒复制。所有感染HCMV的细胞在感染后即刻上清液中均检测到高水平的IL-6。早期滋养层细胞、足月滋养层细胞、JEG-3细胞感染后48h可见IL-6mRNA表达上调。此时,出现了HCMV即刻早期蛋白。在JARS中,未见病毒产生和IL-6mRNA表达上调,而这些感染细胞上清液中的IL-6水平在感染后第6天与模型感染细胞相比显著下降。结论:HCMV复制受滋养层细胞分化程度的影响。人巨细胞病毒感染可上调白介素6的表达,但不依赖于病毒的完全复制。(C)2006爱思唯尔B.V.保留所有权利。
Background: Human cytomegalovirus (hCMV) infection of the trophoblasts is a crucial event in virus transmission from mother to child, being one responsible factor for intrauterine infection of the unborne. Differences of virus replication in trophoblasts depending on time point of pregnancy and degree of differentiation of trophoblasts might influence this transmission. Furthermore, immunological reactions of the trophoblasts to hCMV infection might be important defence mechanisms too. Objectives: hCMV replication and interleukin-6 release in trophoblasts and trophoblast like cells (choriocarcinoma cells) was investigated. Study design: Trophoblasts from term and 1st trimester placentas were isolated and infected with hCMV. hCMV production and release to the supernatant as well as interleukin-6 release and interleukin-6 mRNA production by these infected cells was measured. Choriocarcinoma cell lines (JEG-3, JAR) were treated the same. Non-infected trophoblasts were used as controls. Results: In 1st trimester trophoblast, term trophoblasts and JEG-3 permissive hCMV replication was observed, although with different kinetics and efficiency. In JAR no complete virus replication was seen. High levels of interleukin-6 were measured in the supernatants of all hCMV infected cells immediately after infection. IL-6 mRNA upregulation was seen 48 h after infection in those cell types replication of hCMV occurred (1st trimester trophoblasts, term trophoblasts, JEG-3). At that time-point hCMV immediate early proteins appeared. In JARs no virus production and no IL-6 mRNA upregulation was seen, and IL-6 levels in the supernatant of these hCMV infected cells declined significantely until day 6 after infection compared to mock infected cells. Conclusion: These observations show that hCMV replication is influenced by the degree of trophoblast differentiation. Interleukin-6 is upregulated by hCMV infection, but is independent of complete virus replication. (C) 2006 Elsevier B.V. All rights reserved.