Zhu Ying, Wu Min, Wu Chao-Ying, Xia Ge-Qing
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
J Huazhong Univ Sci Technolog Med Sci. 2013 Oct;33(5):730-734. doi: 10.1007/s11596-013-1188-6. Epub 2013 Oct 20.
The role of progesterone in the Toll-like receptor 4 (TLR4)-MyD88-dependent signaling pathway in pre-eclampsia was studied. Peripheral blood mononuclear cells (PBMCs) from pre-eclampsia (PE) patients were subjected to primary culture, and stimulated with different concentrations of progesterone (0, 10(-8), 10(-6), and 10(-4) mol/L). The mRNA expression of TLR4, MyD88 and nuclear factor-kappaB (NF-κB) was detected by using real-time PCR. The Ikappa-B protein expression was detected by using Western blotting. The expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the supernatant was determined by using ELISA. With the concentrations of progesterone increasing, the mRNA expression levels of TLR4, MyD88 and NF-κB in 2(-ΔΔCT) value were significantly decreased, and the IkappaB protein expression levels were significantly increased. The TNF-α and IL-6 expression showed a downward trend when the progesterone concentration increased, and there were significant differences among all of the groups (P<0.05). It was suggested that progesterone can inhibit the TLR4-MyD88-dependent signaling pathway in PE significantly and benefit for the pregnancy.
研究了孕酮在子痫前期Toll样受体4(TLR4)-髓样分化因子88(MyD88)依赖性信号通路中的作用。对来自子痫前期(PE)患者的外周血单个核细胞(PBMC)进行原代培养,并用不同浓度的孕酮(0、10⁻⁸、10⁻⁶和10⁻⁴mol/L)进行刺激。采用实时定量聚合酶链反应(real-time PCR)检测TLR4、MyD88和核因子κB(NF-κB)的mRNA表达。采用蛋白质免疫印迹法检测IκB蛋白表达。采用酶联免疫吸附测定(ELISA)法测定上清液中肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的表达。随着孕酮浓度的增加,TLR4、MyD88和NF-κB的mRNA表达水平在2⁻ΔΔCT值中显著降低,IκB蛋白表达水平显著升高。当孕酮浓度增加时,TNF-α和IL-6的表达呈下降趋势,各组间差异有统计学意义(P<0.05)。提示孕酮可显著抑制子痫前期患者TLR4-MyD88依赖性信号通路,对妊娠有益。