A Comprehensive Study of the Inhibin/Activin-Family Proteins in Chorioamnionitis

激活素是由抑制素/激活素β亚基组成的二聚体蛋白，其生物学活性受抑制素和活化素结合蛋白的调节。最近，有报道激活素参与炎症反应和伤口愈合。为了研究抑制素/激活素家族蛋白在绒毛膜羊膜炎中的作用，绒毛膜羊膜炎是胎膜早破的主要原因，我们在获得内部审查委员会的许可和患者的知情同意的情况下，使用了人羊膜细胞培养。我们利用DNA芯片和定量聚合酶链式反应分析了羊膜上皮细胞的基因表达，并检测到干扰素诱导基因和与胶原合成或降解相关的基因为二恶英诱导基因。DNA芯片分析显示抑制素/激活素βA亚单位的表达也增加。提示激活素参与了二恶英引起的细胞膜病变。为了研究激活素是否参与膜致密层和成纤维细胞层的炎症反应，对羊膜间充质细胞进行了研究。肿瘤坏死因子-α不增加抑制素/激活素βB亚单位的mRNA，但增加抑制素/激活素βA亚单位的mRNA。酶联免疫吸附试验也显示激活素A蛋白表达增加。炎性细胞因子肿瘤坏死因子-α似乎在mRNA和蛋白水平刺激这些细胞产生激活素A。

Activins are dimeric proteins composed of inhibin/activin beta-subunits, and their biological activities are regulated by inhibins, and activinbinding proteins called follistatins. Recently, the involvement of activins in inflammation and wound healing has been reported. In order to study the role of inhibin/activin family proteins in chorioamnionitis, which is the primary cause of premature rupture of the membranes, we used human amniotic cell culture with the permission of The Internal Review Board and the informed consent of the patients. We studied gene expressions in amniotic epithelial cells by DNA microarray and quantitative PCR analyses, and detected interferon-inducible genes and genes related to collagen synthesis or degradation as dioxin-inducible genes. DNA microarray analysis showed increased expression of the inhibin/activin beta A subunit also. The involvement of activins in the pathology of membranes by dioxins was suggested. In order to study if activins were involved in the inflammation in the compact layer and the fibroblast layer of the membranes, amniotic mesenchymal cells were studied. Tumor necrosis factor-alpha (TNF-alpha) did not increase the inhibin/activin beta B subunit mRNA but did increase the inhibin/activin beta A subunit mRNA. The increase of activin A protein was also shown by enzyme linked immunosorbent assay. Inflammatory cytokine TNF-alpha seemed to stimulate the production of activin A at both mRNA and protein levels in these cells.