A Comprehensive Investigation of the Activin-family in Chorioamnionitis

为了研究激活素在绒毛膜炎中的作用，我们首先测量了原代羊膜上皮细胞培养物中细胞的激活素A分泌。在内部审查委员会的许可和患者的知情同意下，我们在剖宫产期间从没有全身疾病、早产迹象或胎儿并发症的单胎妊娠患者中获得了胎膜样本。羊膜上皮细胞用胰蛋白酶分散并培养。革兰氏阴性细菌细胞壁组分脂多糖和炎性细胞因子肿瘤坏死因子-α都刺激细胞分泌激活素A。因此，激活素似乎参与了绒毛膜炎的病理过程。接下来，为了建立一个全面分析基因表达的系统，我们在2，3，7，8-四氯二苯并对二恶英（TCDD）处理的羊膜上皮细胞培养物中进行了DNA微阵列和定量实时PCR分析。两种分析共鉴定出39个TCDD诱导基因，其中包括CYP 1A 1和CYP 1B 1，这两个基因被认为是典型的TCDD靶基因。此外，干扰素诱导基因和胶原蛋白合成或降解相关基因的表达增强TCDD。绒毛膜炎是胎膜早破的主要原因。另一方面，胎膜的抗张强度由羊膜的胶原蛋白提供。考虑到羊膜的生物学特性和目前的研究结果，在本研究中建立的系统似乎是有用的，在绒毛膜炎的细胞因子，包括激活素家族的基因表达的全面调查。

In order to study the role of activin in chorioamnionitis, we first measured activin A secretion from the cells in primary amniotic epithelia cultures. With the permission of The Internal Review Board and the informed consent of the patients, we obtained fetal membrane samples during cesarean sections, from patients with single pregnancy without systemic disease, signs of premature delivery or fetal complications. Amniotic epithelial cells were dispersed by trypsin and cultured. Both a gram negative bacterial cell wall component lipopolysaccharide and inflammatory cytokine tumor necrosis factor-alpha stimulated the secretion of activin A from the cells. Therefore, activin seemed to be involved in the pathology of chorioamnionitis. Next, to establish a system for comprehensive analysis of gene expression, we performed DNA microarray and quantitative real-time PCR analyses in a 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treated amniotic epithelial cell culture. Thirty nine TCDD-inducible genes, including CYP1A1 and CYP1B1 which are known as the typical TCDD target genes, was identified by both analyses. Furthermore, the expression of interferon-inducible genes and genes related to collagen synthesis or degradation was enhanced by TCDD. Chorioamnionitis is the primary cause of premature rapture of the membrane. On the other hand, the tensile strength of fetal membranes is provided by the collagen of amnion. Considering the biological character of the amnion and the present findings, the system established in the present study seems to be useful in the comprehensive investigation for gene expression of cytokines, including the activin-family, in chorioamnionitis.