Abstract

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.

中文翻译：

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米非司酮通过抑制 TGF-β 表达调控树突状细胞介导的 Tregs 功能

摘要

背景

以前的研究表明，每天低剂量的米非司酮会影响子宫内膜的功能。这些研究还暗示了子宫内膜免疫平衡的改变，这可能与调节子宫内膜功能有关。但具体机制仍有待进一步探索。

方法

在本研究中，FACS 检测了不同浓度米非司酮（20、65 和 200 nM）刺激的树突状细胞 (DC) 中 CD80、CD86 和 ICAM-1 的表达。之后，我们进一步评估了与米非司酮处理的 DC 共培养的 Tregs 中 Forkhead box P3（FOXP3）和 IL-10 的表达。在机制上，我们用酶联免疫吸附试验 (ELISA) 比较了吲哚胺 2,3-双加氧酶 (IDO) 和 TGF-β 的表达。

结果

结果表明，米非司酮以剂量依赖性方式促进CD80、CD86和ICAM-1的表达。相反，与米非司酮处理的 DC 共培养的 Treg 中的 FOXP3 和 IL-10 表达水平与未处理的 DC 共培养的那些相比显着降低。此外，在用米非司酮治疗的 DC 中观察到 IDO 和 TGF-β 表达显着降低。通过使用 IDO 抑制剂（1-甲基色氨酸，1-MT）或 TGF-b 补充剂，我们证实 TGF-β 而不是 IDO 可以挽救与米非司酮处理的 DC 共培养的 Treg 中 FOXP3 和 IL-10 的下调. 所有这些结果表明，米非司酮可能通过降低 TGF-β 表达来调节 DC 功能，这进一步导致 Tregs 中 FOXP3 和 IL-10 的下调。

结论

因此，我们的研究为米非司酮作为一种新型避孕药的潜在临床应用提供了理论基础。