Mifepristone increases the cytotoxicity of uterine natural killer cells by acting as a glucocorticoid antagonist via ERK activation.

PloS One
Yuezhou ChenLi-Li Huang

Abstract

Mifepristone (RU486), a potent antagonist of progesterone and glucocorticoids, is involved in immune regulation. Our previous studies demonstrated that mifepristone directly augments the cytotoxicity of human uterine natural killer (uNK) cells. However, the mechanism responsible for this increase in cytotoxicity is not known. Here, we explored whether the increased cytotoxicity in uNK cells produced by mifepristone is due to either anti-progesterone or anti-glucocorticoid activity, and also investigated relevant changes in the mitogen-activated protein kinase (MAPK) pathway. Uterine NK cells were isolated from decidual samples and incubated with different concentrations of progesterone, cortisol, or mifepristone. The cytotoxicity and perforin expression of uNK cells were detected by mitochondrial lactate dehydrogenase-based MTS staining and flow cytometry assays, respectively. Phosphorylation of components of the MAPK signaling pathway was detected by Western blot. Cortisol attenuated uNK cell-mediated cytotoxicity in a concentration-dependent manner whereas progesterone had no effect. Mifepristone alone increased the cytotoxicity and perforin expression of uNK cells; these effects were blocked by cortisol. Furthermore, mifepri...Continue Reading

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Citations

Nov 2, 2014·Journal of Agricultural and Food Chemistry·Qi LiQing-Sheng Huang
Oct 5, 2014·International Immunopharmacology·Ting HuyanPeng Shang
Aug 8, 2013·Astrobiology·Qi LiQingsheng Huang
Sep 17, 2013·Environmental Toxicology and Pharmacology·Qi LiQingsheng Huang
May 3, 2014·Expert Opinion on Pharmacotherapy·Giuseppe BenagianoIvo Brosens
May 31, 2014·BioMed Research International·Sheau-Fang YangYao-Tsung Yeh
Mar 12, 2015·Immunobiology·Qi LiQing-Sheng Huang
May 31, 2016·Journal of Pregnancy·Kameliya VinketovaTsvetelina Oreshkova
Mar 10, 2017·Trends in Endocrinology and Metabolism : TEM·Shannon Whirledge, John A Cidlowski
Jul 6, 2018·Frontiers in Immunology·Nishel M ShahMark R Johnson
May 23, 2021·International Immunopharmacology·Qi LiWei Zhang

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Methods Mentioned

BETA
biopsy
density-gradient centrifugation
flow cytometry
contraception

Software Mentioned

Quantity One
SPSS

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