Kline J N, Geist L J, Monick M M, Stinski M F, Hunninghake G W
Department of Medicine, University of Iowa College of Medicine, Iowa City 52242.
J Immunol. 1994 Mar 1;152(5):2351-7.
Human cytomegalovirus (HCMV), which is a major cause of morbidity and mortality in immunosuppressed patients, can itself alter immune function. It has previously been shown that HCMV immediate early (IE) gene products regulate the IL-1 beta promoter. The purpose of these studies was to determine whether HCMV IE gene products regulate expression of the IL-1 receptor antagonist (IL-1ra) gene. THP-1 cells, a myelomonocytic cell line, were transfected with a plasmid containing one or more of the HCMV IE genes downstream of the HCMV major immediate early promoter, or with a control plasmid. IL-1 beta and IL-1ra protein secretion was evaluated by ELISA, and expression of the mRNA for the cytokines was examined by means of Northern blot analysis. The HCMV IE1+2 gene products were found to increase expression of the mRNA for both IL-1 beta and IL-1ra; however, only the IL-1ra protein was released in increased amounts. The individual HCMV IE gene products had different effects on expression of the IL-1ra gene; the HCMV IE1 gene product down-regulated expression of the IL-1ra gene, whereas the IE2 gene product up-regulated expression of the IL-1ra gene. Thus, HCMV IE gene products can either up-regulate or down-regulate expression of the IL-1ra gene, depending on which IE genes are expressed in monocytes-macrophages. This study adds to the understanding of how HCMV can alter immune function during both active and latent infection.
人巨细胞病毒（HCMV）是免疫抑制患者发病和死亡的主要原因，它本身可改变免疫功能。此前已有研究表明，HCMV立即早期（IE）基因产物可调节白细胞介素-1β（IL-1β）启动子。这些研究的目的是确定HCMV IE基因产物是否调节白细胞介素-1受体拮抗剂（IL-1ra）基因的表达。将髓单核细胞系THP-1细胞用含有一个或多个HCMV IE基因且位于HCMV主要立即早期启动子下游的质粒或对照质粒进行转染。通过酶联免疫吸附测定（ELISA）评估IL-1β和IL-1ra蛋白分泌情况，并通过Northern印迹分析检测细胞因子mRNA的表达。发现HCMV IE1 + 2基因产物可增加IL-β和IL-1ra mRNA的表达；然而，只有IL-1ra蛋白的释放量增加。单个HCMV IE基因产物对IL-1ra基因的表达有不同影响；HCMV IE1基因产物下调IL-1ra基因的表达，而IE2基因产物上调IL-1ra基因的表达。因此，HCMV IE基因产物可上调或下调IL-1ra基因的表达，这取决于单核细胞 - 巨噬细胞中表达的是哪些IE基因。这项研究有助于进一步了解HCMV在活跃感染和潜伏感染期间如何改变免疫功能。
