Liu Jia, Dong Peng, Jia Ningyi, Wen Xi, Luo Lanrong, Wang Shijun, Li Jian
Department of Obstetrics and Gynecology, Xuanwu Hospital, Capital Medical University, Beijing, China.
Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.
J Matern Fetal Neonatal Med. 2022 Aug;35(16):3209-3215. doi: 10.1080/14767058.2020.1817369. Epub 2020 Sep 9.
This study aims to investigate the expression levels of TNF-α, IFN-γ, IL-4, and IL-10 in dNK cells and determine whether or not the MAPK signal pathway is involved in the regulation of cytokine secretion by dNK cells at the maternal-fetal interface.
In this study, we collected decidua specimens from patients with apparently normal pregnant and unexplained recurrent pregnancy loss (URPL) and extracted dNK cells by enzymatic digestion. Then the expression of cytokines were analyzed by flow cytometry and Real-Time PCR respectively.
The secretions of both IFN-γ and TNF-α in dNK cells in URPL were significantly higher than those in normal pregnancy. Furthermore, p38/MAPK inhibitors can inhibit the secretion of four cytokines in normal pregnancy, while in URPL cases, p38/MAPK inhibitors only significantly inhibit the secretion of IL-4 and IFN-γ. ERK inhibitors had no effect on the expression of all four cytokines and JNK/MAPK inhibitors varied on different cytokines.
URPL is associated with a NK1 cytokine profile. MAPK signaling pathway is involved in the regulation of cytokine secretion by decidual NK cells at maternal-fetal interface.
本研究旨在探讨肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)和白细胞介素-10(IL-10)在蜕膜自然杀伤(dNK)细胞中的表达水平,并确定丝裂原活化蛋白激酶(MAPK)信号通路是否参与母胎界面处dNK细胞细胞因子分泌的调节。
在本研究中,我们收集了妊娠情况看似正常的患者以及不明原因复发性流产(URPL)患者的蜕膜标本,并通过酶消化法提取dNK细胞。然后分别通过流式细胞术和实时荧光定量聚合酶链反应(Real-Time PCR)分析细胞因子的表达。
URPL患者dNK细胞中IFN-γ和TNF-α的分泌均显著高于正常妊娠者。此外,p38/MAPK抑制剂可抑制正常妊娠中四种细胞因子的分泌,而在URPL病例中,p38/MAPK抑制剂仅显著抑制IL-4和IFN-γ的分泌。细胞外信号调节激酶(ERK)抑制剂对所有四种细胞因子的表达均无影响,而c-Jun氨基末端激酶(JNK)/MAPK抑制剂对不同细胞因子的影响各异。
URPL与NK1细胞因子谱相关。MAPK信号通路参与母胎界面处蜕膜自然杀伤细胞细胞因子分泌的调节。