Background: Previous studies have demonstrated that mifepristone in the daily low-dose affects the function of endometrium. These researches also implied an alteration of endometrium immune balance, which might be involved in regulating endometrial function. However, the detailed mechanisms remain to be further explored.
Methods: In this study, the expressions of CD80, CD86, and ICAM-1 in dendritic cells (DCs), which were stimulated with different concentrations of mifepristone (20, 65, and 200 nM), were detected by FACS. After that, we further evaluated the expression of Forkhead box P3 (FOXP3) and IL-10 in Tregs, which co-cultured with mifepristone treated DCs. In mechanism, we compared the indoleamine 2,3-dioxygenase (IDO) and TGF-β expression with enzyme-linked immunosorbent assay (ELISA).
Results: The results indicated that mifepristone promoted the expressions of CD80, CD86, and ICAM-1 in a dosage dependent manner. Reversely, FOXP3 and IL-10 expression levels in Tregs co-cultured with mifepristone-treated DCs were significantly decreased compared with those co-cultured with nontreated DC. Furthermore, a significant reduce in IDO and TGF-β expression was observed in DCs treated with mifepristone. By using the IDO inhibitor (1-methyl tryptophan, 1-MT) or TGF-b supplement, we confirmed that TGF-β, but not IDO could rescue the downregulation of FOXP3 and IL-10 in Tregs co-cultured with mifepristone treated DCs. All of these results suggest that mifepristone may regulate DC function by decreasing TGF-β expression, which further results in the downregulations of FOXP3 and IL-10 in Tregs.
Conclusion: Therefore, our research provides a theoretical basis for a potentially clinical application of mifepristone as a novel contraceptive.
Keywords: IDO; Mifepristone; TGF-β; Tregs; dendritic cells; immunomodulatory.