Problem: Uterine natural killer cells (uNK) do not express progesterone receptor, but express glucocorticoid receptor (GR). So, we speculate that progesterone may regulate uNK cells through a GR-mediated process.
Method of study: After mouse NK cells were stimulated with CpG with or without IL-12 in the presence or absence pre-treatment of progesterone, the effects of progesterone on NK via GR were investigated by using RU486 (progesterone receptor and GR antagonist) and CDB-2914 (progesterone receptor antagonist). The expressions of CD69 and IFN-γ were determined by flow cytometry and qPCR. Phosphorylation of IκB and STAT4 was determined by Western blot. Furthermore, we purified uNK cells from human decidual tissues using anti-CD56 microbeads to verify the effect of progesterone on uNK via GR.
Results: Progesterone suppressed CD69 and IFN-γ expression of mouse spleen NK cells and human uNK cells induced by CpG combined with IL-12. CDB-2914 had no effect on IFN-γ expression suppressed by progesterone, while RU486 could abolish the inhibitory effect of progesterone. In addition, progesterone could decrease the phosphorylation of both STAT4 and IκB.
Conclusions: In the present study, we first prove that progesterone can regulate NK cells via GR. It is valuable for further understanding the role of uNK in progesterone regulated gestation process.
© 2012 John Wiley & Sons A/S.