孕酮和IL-15对人早孕蜕膜子宫自然杀伤(uNK)细胞促血管生成因子的调节

Effect of Progesterone and Interleukin-15 on Angiogenic Growth Factor of the Decidual Uterine Natural Killer Cells in Early Pregnancy

目的:探讨孕酮和IL-15对蜕膜子宫自然杀伤细胞(uNK)在早孕蜕膜血管生成/重塑过程中的作用。方法:免疫磁珠(MACS)分离及纯化蜕膜uNK细胞后进行体外培养,分别用不同浓度孕酮或IL-15干预72h后获取培养上清液和细胞。采用RT-PCR和ELISA检测蜕膜uNK细胞的VEGF-A、VEGF-C、Ang2的mRNA转录和蛋白表达。结果:蜕膜uNK细胞可表达多种与血管形成有关的生物活性分子,与未干预的空白对照组相比,IL-15促进uNK细胞表达VEGF-A、VEGF-C(P<0.05),且呈剂量依赖关系,但对Ang2无影响;而孕酮对uNK细胞表达上述因子均无显著影响(P>0.05)。结论:妊娠早期蜕膜uNK细胞通过表达多种促血管生成因子,在早孕蜕膜血管生成/重塑中起着重要的作用,IL-15对此有直接促进作用。

Objective： To explore the effects of progesterone（P） and interleukin-15（IL-15） on decidual uterine natural killer cell （uNK cell） of early pregnancy. Methods： CD56-microbeads （MACS） were used to isolate and purify uNK cells from human decidua of normal early pregnancy, and then cultured in vitro. These uNK cells were treated with P or IL-15 in different concentrations at least three holes for each concentration. After treated 72 h, ELISA and RT-PCR were used to detect the expression of VEGF-A, VEGF-C, and Ang2 in these uNK cells on their supernatant. Results： These decidual uNK cells expressed multi-angiogenic growth factors. IL-15 enhanced the gene or protein expression of VEGF-A/VEGF-C of decidual uNK cells in a dose-dependent manners （P〈0.05）, but no impact on Aug2 expression. However, P had no effect on gene expression of these angiogenic growth factors in decidual uNK cells, neither in protein level （P〉0.05）. Conclusion： uNK cells play an important role in the angiogenesis of human decidua in early pregnancy, through expressing multiple angiogenic growth factors, which are promoted by IL-15 directly.