Macrophages promote the growth and invasion of endometrial stromal cells by downregulating IL-24 in endometriosis

Jun Shao, Bing Zhang, Jiajun Yu, Jia-Jun Yu, Chun-Yan Wei, Chunyan Weı, Wen-Jie Zhou, Wen‐Jie Zhou, Kai‐Kai Chang, Kai-Kai Chang, Hui-Li Yang, Hui‐Li Yang, Li-Ping Jin, Liping Jin, Xiao-Yong Zhu, Xiao‐Yong Zhu, Ming‐Qing Li, Ming-Qing Li
Reproduction (Cambridge, England) · 2016 · vol. 152(6) , pp. 673–682 · doi:10.1530/rep-16-0278 · PMID:27624484 · W2519030441
article OA: bronze CC0 ⤵ 34 in-corpus citations
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Macrophages reduce IL-24 expression in endometrial stromal cells, promoting their proliferation and invasion, which contributes to endometriosis development.

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Abstract

Macrophages play an important role in the origin and development of endometriosis. Estrogen promoted the growth of decidual stromal cells (DSCs) by downregulating the level of interleukin (IL)-24. The aim of this study was to clarify the role and mechanism of IL-24 and its receptors in the regulation of biological functions of endometrial stromal cells (ESCs) during endometriosis. The level of IL-24 and its receptors in endometrium was measured by immunohistochemistry. In vitro analysis was used to measure the level of IL-24 and receptors and the biological behaviors of ESCs. Here, we found that the expression of IL-24 and its receptors (IL-20R1 and IL-20R2) in control endometrium was significantly higher than that in eutopic and ectopic endometrium of women with endometriosis. Recombinant human IL-24 (rhIL-24) significantly inhibited the viability of ESCs in a dosage-dependent manner. Conversely, blocking IL-24 with anti-IL-24 neutralizing antibody promoted ESCs viability. In addition, rhIL-24 could downregulate the invasiveness of ESCs in vitro After co-culture, macrophages markedly reduced the expression of IL-24 and IL-20R1 in ESCs, but not IL-22R1. Moreover, macrophages significantly restricted the inhibitory effect of IL-24 on the viability, invasion, the proliferation relative gene Ki-67, proliferating cell nuclear antigen (PCNA) and cyclooxygenase2 (COX-2), and the stimulatory effect on the tumor metastasis suppressor gene CD82 in ESCs. These results indicate that the abnormally low level of IL-24 in ESCs possibly induced by macrophages may lead to the enhancement of ESCs' proliferation and invasiveness and contribute to the development of endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Cell Movement Endometriosis Endometrium Interleukins Macrophages Stromal Cells Adult Cell Proliferation Coculture Techniques Endometriosis Endometriosis Endometrium Endometrium Female Humans Interleukin-24 Interleukins Interleukins Macrophages Macrophages

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