Endometrial stromal cells treated by tumor necrosis factor-α stimulate macrophages polarized toward M2 via interleukin-6 and monocyte chemoattractant protein-1

This study aimed to investigate the effects of endometrial stromal cells (ESC)-derived interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 on macrophage polarization in endometriosis.

In endometriosis patients, the macrophages of the eutopic endometrium polarize toward M1 compared with the normal endometrium, and those of the ectopic endometrium were mainly M2-polarized. Under the action of TNF-α, ESC-derived IL-6 and MCP-1 could stimulate peritoneal macrophages toward M2-polarization, which could modulate endometriosis.

Macrophage polarization was measured in eutopic endometrium of control participants ('normal endometrium'), eutopic endometrium of patients with endometriosis ('eutopic endometrium') and ectopic endometrium of endometriosis patients ('ectopic endometrium') by immunohistochemical staining. Expression of IL-6 and MCP-1 were measured in the eutopic and ectopic endometrium through enzyme-linked immunosorbent assays. Expression of CD163 was measured in human acute monocytic leukemia (THP-1) cell-derived macrophages that were treated with conditional medium induced by tumor necrosis factor (TNF)-α, TNF-α + anti-IL-6 or TNF-α + anti-MCP-1 via flow cytometry.

The ratio of CD163+/CD68+ macrophages in the normal endometrium was higher than that in the eutopic endometrium, while differences between the eutopic and ectopic endometrium were not statistically significant. IL-6 and MCP-1 exhibited enhanced expression in the ectopic endometrium group and decreased expression in the eutopic endometrium group. TNF-α could promote the expression of ESC-derived IL-6 and MCP-1. Intervention with TNF-α-induced conditioned medium resulted in the upregulation of CD163 in THP-1 cells, while conditional medium induced with IL-6 and MCP-1 neutralizing antibodies decreased the proportion of CD163+ macrophages significantly.