Progesterone Enhances Immunoregulatory Activity of Human Mesenchymal Stem Cells Via PGE2 and IL‐6

Abstract

Progesterone (P4) plays a central role in the establishment and maintenance of pregnancy. It also has profound effects on the regulation of immune responses. Mesenchymal stem cells (MSCs), which are thought to have the ability to modulate immunocyte activation, are present in human endometrium and deciduas and highly express progesterone receptor (PR). Especially, during pregnancy, both P4 and MSCs are present and regulatively changed at the fetal-maternal interface, but the effect of P4 on the MSCs remains unknown. Therefore, in this study, we investigated the effects of P4 on the immunomodulatory ability of MSCs and the underlying mechanisms. Mesenchymal stem cells were obtained from human umbilical cords. The effects of P4 on the cell morphology, phenotype, proliferation, apoptosis, and expression levels of cytokine and protein were examined. Progesterone did not affect the phenotype, morphology, proliferation, and apoptosis of MSCs, but promoted the production of PGE2 and IL-6 in MSCs. Furthermore, the up-regulation of PGE2 and IL-6 was related to the activation of p38 and NF-κB. Progesterone enhances immunomodulatory function of MSCs through up-regulation of PGE2 and IL-6. The data suggest that P4-regulated MSCs may play a crucial role in modulating the local immune balance of fetal-maternal interface.