Mifepristone Augments uNK Cell-Cytotoxicity Figure 7. Upregulation of perforin expression by mifepristone was inhibited by PD98059 or U0126. Before the treatment with cortisol 6 mifepristone, uNK cells were pretreated with PD98059 (A) or U0126 (B) for 30 min. They were then treated with mifepristone 6 cortisol for 24 h. Cells stimulated with IL-15 were used as positive control. Perforin expression in uNK cells was examined by flow cytometry. The value is the percent of perforin-positive cells in the total number of uNK cells. Data were analyzed using ANOVA and expressed as means 6 SEM. *, P,0.05. doi:10.1371/journal.pone.0036413.g007 highly dependent on perforin [45]. It has been reported that the mobilization and redistribution of perforin play an important role in the control of NK cytotoxicity [46]. In a previous study, we showed that in human endometrial explants, mifepristone increased expression of perforin and increased uNK cell-mediated cytotoxicity [14]. In the current study, we observed that the mifepristone-induced increase in perforin expression in uNK cells can be reversed by cortisol, which indicated that mifepristone could increase the expression of perforin through the GR. Glucocorticoids are known to show an immunosuppressive effect in lymphocytes. In the clinic, glucocorticoids work as immunosuppressive drugs to impair NK-cell function by affecting PLoS ONE | www.plosone.org 8 May 2012 | Volume 7 | Issue 5 | e36413