Gill Ryan M, Ni Jian, Hunt Joan S
Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160-7400, USA.
Am J Pathol. 2002 Dec;161(6):2011-7. doi: 10.1016/S0002-9440(10)64479-3.
mRNA encoding LIGHT (homologous to lymphotoxins, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed by T lymphocytes), a member of the tumor necrosis factor superfamily of ligands, as well as mRNAs encoding LIGHT receptors [HVEM, LTbetaR, and TR6 (DcR3)] are present in placentas and cytotrophoblast cells at term. To establish translation of these messages and determine directions for functional studies, term placentas, amniochorion membranes, and purified cytotrophoblast cells were evaluated by immunoblotting and immunohistochemistry. Ligand and receptor proteins were identified in lysates from all three sources although the soluble receptor, TR6, was scarce in placentas and all receptors were in low abundance in cytotrophoblast cells. These results were confirmed and cell type-specific expression was documented by immunohistochemistry. Ligand and receptor proteins were differentially expressed according to cell type. For example, HVEM was identified on syncytiotrophoblast but not in villous mesenchymal cells; amnion epithelial cells were positive for all proteins whereas chorion membrane cytotrophoblasts exhibited none. Because LIGHT is a powerful cytokine that can alter gene expression and promote apoptosis, these experiments suggest that ligand-receptor interactions may critically influence structural and functional aspects of human placentas through as yet undefined autocrine/paracrine pathways.
编码LIGHT(与淋巴毒素同源,表现出诱导性表达,与单纯疱疹病毒糖蛋白D竞争T淋巴细胞表达的受体HVEM)的信使核糖核酸(mRNA),它是肿瘤坏死因子超家族配体的成员之一,以及编码LIGHT受体[HVEM、LTβR和TR6(DcR3)]的mRNA在足月胎盘和细胞滋养层细胞中均有存在。为了确定这些信息的翻译情况并为功能研究指明方向,通过免疫印迹法和免疫组织化学对足月胎盘、羊膜绒毛膜和纯化的细胞滋养层细胞进行了评估。在所有三种来源的裂解物中均鉴定出了配体和受体蛋白,不过可溶性受体TR6在胎盘中含量稀少,且所有受体在细胞滋养层细胞中的丰度都很低。这些结果得到了证实,免疫组织化学记录了细胞类型特异性表达情况。配体和受体蛋白根据细胞类型呈现出差异表达。例如,在合体滋养层上鉴定出了HVEM,但在绒毛间充质细胞中未鉴定出;羊膜上皮细胞对所有蛋白均呈阳性,而绒毛膜细胞滋养层细胞则均未显示阳性。由于LIGHT是一种强大的细胞因子,能够改变基因表达并促进细胞凋亡,这些实验表明配体 - 受体相互作用可能通过尚未明确的自分泌/旁分泌途径对人胎盘的结构和功能方面产生关键影响。