Lee Jeong Yeon, Kim Hyunju
Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Republic of Korea.
Curr Issues Mol Biol. 2024 Jul 12;46(7):7386-7394. doi: 10.3390/cimb46070438.
Trophoblasts, the principal cellular component of the placenta, play an important role in nutrient and gas exchange. Previous studies have indicated that maternal immune activation (MIA) leads to an elevation in IL-17A cytokine levels in maternal serum, subsequently influencing fetal brain development during pregnancy. In this study, we aimed to elucidate the impact of the IL-17A cytokine on placental function. First, we treated JAR and JEG-3, which is a placenta cell line, with IL-17A in a concentration-dependent or time-dependent manner and observed cell morphology and viability. It was confirmed that treatment with IL-17A or a double-stranded RNA mimic (PolyI:C) had no effect on the morphology or cell viability. IL-17A treatment increased the expression of IL-17R at the mRNA and protein levels, and Poly(I:C) increased the levels of IFNγ and TNFα. Additionally, PPARγ, known as a metabolism regulator, was increased by IL-17A treatment. Also, we observed that the expression of Glut1 and Glut3 was increased by IL-17A treatment. To confirm this, we examined the expression of transporters in the placental tissue of the MIA rodent model, and we observed that mRNA expression of glut1 and glut3 was significantly increased. However, the expression of Gltu1 and Glut3 was observed to be significantly inhibited in the brains of MIA-induced offspring. This study suggests that IL-17A increases signaling through IL-17R in the placenta and fetal brain tissue; however, there is a mechanism for regulating the expression of glucose transporters by increased IL-17A in the placenta.
滋养层细胞是胎盘的主要细胞成分，在营养物质和气体交换中起重要作用。先前的研究表明，母体免疫激活（MIA）会导致母体血清中白细胞介素-17A（IL-17A）细胞因子水平升高，进而影响孕期胎儿大脑发育。在本研究中，我们旨在阐明IL-17A细胞因子对胎盘功能的影响。首先，我们以浓度依赖性或时间依赖性方式用IL-17A处理胎盘细胞系JAR和JEG-3，并观察细胞形态和活力。结果证实，用IL-17A或双链RNA模拟物（PolyI:C）处理对细胞形态或活力没有影响。IL-17A处理可增加IL-17R在mRNA和蛋白质水平的表达，而Poly(I:C)可增加IFNγ和TNFα的水平。此外，作为代谢调节剂的过氧化物酶体增殖物激活受体γ（PPARγ）通过IL-17A处理而增加。同时，我们观察到IL-17A处理可增加葡萄糖转运蛋白1（Glut1）和葡萄糖转运蛋白3（Glut3）的表达。为了证实这一点，我们检测了MIA啮齿动物模型胎盘组织中转运蛋白的表达，发现glut1和glut3的mRNA表达显著增加。然而，在MIA诱导的后代大脑中，观察到Gltu1和Glut3的表达受到显著抑制。本研究表明，IL-17A可增强胎盘和胎儿脑组织中通过IL-17R的信号传导；然而，胎盘中IL-17A增加存在调节葡萄糖转运蛋白表达的机制。
