Jarvis James N, Dozmorov Igor, Jiang Kaiyu, Chen Yanmin, Frank Mark Barton, Cadwell Craig, Turner Sean, Centola Michael
Department of Pediatrics, Pediatric Rheumatology Research, Basic Sciences Ed. Building #235A, University of Oklahoma College of Medicine, Oklahoma City, OK 73104, USA.
J Reprod Immunol. 2004 Apr;61(2):99-113. doi: 10.1016/j.jri.2003.12.003.
The immunologic adaptations of pregnancy have come under increasing scrutiny in the past 15 years. Existing experimental evidence clearly demonstrates that placental trophoblasts play an important role in regulating immunologic/inflammatory responses at the maternal-fetal interface. We used a well-developed gene expression array to examine in greater detail the physiologic response of trophoblast-like choriocarcinoma cells to a model immunologic 'challenge.' We co-cultured PHA-activated or resting peripheral blood mononuclear cells (PBMC) with the human choriocarcinoma cell line JAR for time periods ranging from 2 to 18 h. Messenger RNA expression in the JAR cells was then assessed using a 21,329-gene microarray and novel biostatistical analyses that we have previously published. Patterns of differential gene expression were assessed using a commercial pathway analysis software program. Differences in gene expression between JAR cells cultured with activated PBMC (experimental samples) and JAR cells cultured with resting PBMC (control samples) were seen only at the 2h time point. That is, multiple genes were transcribed in JAR cells in response to activated PBMC, but expression levels of the genes had all returned to baseline by 6h. Molecular modeling demonstrated that the differentially expressed genes were largely associated with cell growth and differentiation. This model was confirmed by noting a two-fold increase in CD10/neutral endopeptidase expression (a marker for cell differentiation) in JAR cells incubated with media from activated PBMC compared with JAR cells incubated with resting PBMC. These findings support the hypothesis that there is a delicate immunologic milieu at the maternal-fetal interface that must be maintained. Immunologic/inflammatory challenge at the maternal-fetal interface is compensated by cellular mechanisms that work to reduce inflammation and rapidly restore immunologic balance.
在过去15年里，孕期的免疫适应性受到了越来越多的审视。现有的实验证据清楚地表明，胎盘滋养层细胞在调节母胎界面的免疫/炎症反应中发挥着重要作用。我们使用一种成熟的基因表达阵列，更详细地研究滋养层样绒毛膜癌细胞对模拟免疫“挑战”的生理反应。我们将PHA激活的或静息的外周血单个核细胞（PBMC）与人类绒毛膜癌细胞系JAR共培养2至18小时。然后使用我们之前发表的一个包含21329个基因的微阵列和新的生物统计学分析方法，评估JAR细胞中的信使核糖核酸表达。使用商业通路分析软件程序评估差异基因表达模式。在用激活的PBMC培养的JAR细胞（实验样本）和用静息的PBMC培养的JAR细胞（对照样本）之间，仅在2小时时间点观察到基因表达差异。也就是说，JAR细胞中多个基因因激活的PBMC而转录，但这些基因的表达水平在6小时时均已恢复到基线。分子建模表明，差异表达的基因主要与细胞生长和分化相关。通过观察与用激活的PBMC培养基孵育的JAR细胞相比，与用静息的PBMC培养基孵育的JAR细胞中CD10/中性内肽酶表达（细胞分化标志物）增加了两倍，证实了该模型。这些发现支持了这样一种假设，即母胎界面存在一个必须维持的微妙免疫环境。母胎界面的免疫/炎症挑战通过旨在减轻炎症并迅速恢复免疫平衡的细胞机制得到补偿。
