Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China; Laboratory of Environmental Toxicology, Anhui Medical University, Hefei, China.
Department of Toxicology, School of Public Health, Anhui Medical University, Hefei, China; Laboratory of Environmental Toxicology, Anhui Medical University, Hefei, China.
Placenta. 2018 May;65:7-14. doi: 10.1016/j.placenta.2018.03.008. Epub 2018 Mar 28.
Several reports demonstrated that cadmium (Cd) had proinflammatory activities. The present study aimed to investigate whether Cd induces inflammatory cytokines in mouse placenta and human trophoblast cells.
Human JEG-3 cells were treated with different concentration of CdCl (0-50 μM) or CdCl (25 μM) for different times. The pregnant mice were administered with CdCl (3.0 mg/kg, i.p.) on GD15.
TNF-α, IL-8 and IL-6 mRNAs were elevated in CdCl-treated JEG-3 cells. Several inflammatory cytokines were up-regulated in Cd-treated placenta of mice. Moreover, keratinocyte chemokine (KC), a functional analogue of human IL-8, was increased in maternal serum and amniotic fluid from CdCl-exposed mice. Additional experiment showed that gestational Cd exposure activated Akt signaling in mouse placenta. Co-culture with CdCl elevated pAkt level in JEG-3 cells in concentration- and time-dependent manners. LY294002, a specific inhibitor of PI3K, blocked CdCl-evoked Akt phosphorylation in JEG-3 cells. Concomitantly, LY294002 inhibited CdCl-induced IL-8 in JEG-3 cells. N-acetylcysteine (NAC), an antioxidant and a glutathione precursor, blocked CdCl-evoked Akt phosphorylation in mouse placenta and human trophoblast cells. Additionally, NAC attenuated Cd-induced up-regulation of KC in amniotic fluid.
Cd induces inflammatory cytokines partially through activating Akt signaling in mouse placenta and human trophoblast cells. NAC may be exploited for prevention of Cd-induced placental inflammation.
多项报告表明，镉（Cd）具有促炎活性。本研究旨在探讨 Cd 是否会诱导小鼠胎盘和人滋养层细胞中的炎症细胞因子。
用不同浓度的 CdCl（0-50μM）或 CdCl（25μM）处理人 JEG-3 细胞不同时间。在 GD15 时，用 CdCl（3.0mg/kg，腹腔注射）处理怀孕小鼠。
CdCl 处理的 JEG-3 细胞中 TNF-α、IL-8 和 IL-6mRNA 升高。Cd 处理的小鼠胎盘中几种炎症细胞因子上调。此外，角质细胞趋化因子（KC），一种人 IL-8 的功能类似物，在 CdCl 暴露的母鼠血清和羊水增加。进一步的实验表明，妊娠期 Cd 暴露激活了小鼠胎盘的 Akt 信号通路。与 CdCl 共培养以浓度和时间依赖的方式增加了 JEG-3 细胞中的 pAkt 水平。PI3K 的特异性抑制剂 LY294002 阻断了 JEG-3 细胞中 CdCl 诱导的 Akt 磷酸化。同时，LY294002 抑制了 CdCl 诱导的 JEG-3 细胞中 IL-8 的产生。N-乙酰半胱氨酸（NAC），一种抗氧化剂和谷胱甘肽前体，阻断了 CdCl 诱导的小鼠胎盘和人滋养层细胞中 Akt 的磷酸化。此外，NAC 减弱了 Cd 诱导的羊水 KC 上调。
Cd 通过激活小鼠胎盘和人滋养层细胞中的 Akt 信号通路诱导炎症细胞因子的产生。NAC 可用于预防 Cd 诱导的胎盘炎症。
