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

Xuemin Qiu, Xue-Min Qiu, Zhen‐Zhen Lai, Zhen-Zhen Lai, Siyao Ha, Si-Yao Ha, Hui-Li Yang, Hui‐Li Yang, Libing Liu, Li-Bing Liu, Yan Wang, Jia-Wei Shi, Jiawei Shi, Lu-Yu Ruan, Lu‐Yu Ruan, Jiang-Feng Ye, Jiang‐Feng Ye, Jiang‐Nan Wu, Jiang-Nan Wu, Qiang Fu, Xiaofang Yi, Xiao-Fang Yi, Kai‐Kai Chang, Kai-Kai Chang, Ming-Qing Li, Ming‐Qing Li
Reproduction (Cambridge, England) · 2019 · vol. 159(3) , pp. 251–260 · doi:10.1530/rep-19-0411 · PMID:31869309 · W2998619267
article OA: bronze CC0 ⤵ 23 in-corpus citations
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Interleukin-2 and -27 synergistically promote endometriotic stromal cell growth and invasion by modulating the balance of IFN-γ and IL-10 in endometriosis.

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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.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Interferon-gamma Interleukins T-Lymphocytes Adult Ascitic Fluid Ascitic Fluid Endometriosis Endometriosis Female Humans Interferon-gamma Interleukin-10 Interleukin-10 Interleukin-2 Interleukin-2 Interleukins Primary Cell Culture Stromal Cells Stromal Cells

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