IL-2 and IL-27 synergistically promote growth and invasion of endometriotic stromal cells by maintaining the balance of IFN-γ and IL-10 in endometriosis.

Abstract

Immune cells and cytokines have important roles in the pathogenesis of endometriosis. However, the production and role of cytokines of T helper type 1 (Th1) and Th2 cells in the progress of endometriosis have remained to be fully elucidated. The present study reported that the interferon (IFN)-γ levels and the percentage of IFN-γ+CD4+ cells were significantly increased in the peritoneal fluid (PF) at the early stage and maintained at a higher level at the advanced stage of endometriosis; furthermore, interleukin (IL)-10 and IL-10+CD4+ cells were elevated in the advanced stage of endometriosis. In addition, IL-2 levels in the PF at the advanced stage of endometriosis were elevated and negatively associated with IFN-γ expression. In a co-culture system of ectopic endometrial stromal cells (ESCs) and macrophages, elevated IL-2 was observed, and treatment with cytokines IL-2 and transforming growth factor-β led to upregulation of the ratio of IL-2+ macrophages. IL-27-overexpressing ESCs and macrophages were able to induce a higher ratio of IL-10+CD4+ T cells. Blocking of IL-2 with anti-IL-2 neutralizing antibody led to upregulation of the ratio of IFN-γ+CD4+ T cells in the co-culture system in vitro. Recombinant human IL-10 and IFN-γ promoted the viability, invasiveness and transcription levels of matrix metalloproteinase (MMP)2, MMP9, and prostaglandin-endoperoxide synthase 2 of ESCs, particularly combined treatment with IL-10 and IFN-γ. These results suggest that IL-2 and IL-27 synergistically promote the growth and invasion of ESCs by modulating the balance of IFN-γ and IL-10 and contribute to the progress of endometriosis.

• Authors: Xue-Min Qiu, Zhen-Zhen Lai, Si-Yao Ha, Hui-Li Yang, Li-Bing Liu, Yan Wang, Jia-Wei Shi, Lu-Yu Ruan, Jiang-Feng Ye, Jiang-Nan Wu, Qiang Fu, Xiao-Fang Yi, Kai-Kai Chang, Ming-Qing Li
• Journal: Reproduction (Cambridge, England) (Reproduction) Vol. 159 Issue 3 Pg. 251-260 (03 2020) ISSN: 1741-7899 [Electronic] England
• PMID: 31869309 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• IL10 protein, human
• IL2 protein, human
• Interleukin-2
• Interleukins
• MYDGF protein, human
• Interleukin-10
• Interferon-gamma

Topics

• Adult
• Ascitic Fluid (metabolism)
• Endometriosis (immunology, metabolism)
• Female
• Humans
• Interferon-gamma (metabolism)
• Interleukin-10 (metabolism)
• Interleukin-2 (metabolism)
• Interleukins (metabolism)
• Primary Cell Culture
• Stromal Cells (physiology)
• T-Lymphocytes (metabolism)