Macrophages promote the growth and invasion of endometrial stromal cells by downregulating IL-24 in endometriosis.
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.
Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology.
Jun
J
Shao
Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology.
Bing
B
Zhang
Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology.
Jia-Jun
JJ
Yu
Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology.
Chun-Yan
CY
Wei
Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology.|Key Laboratory of Reproduction Regulation of NPFPCSIPPR, IRD, Fudan University, Shanghai, People's Republic of China.
Wen-Jie
WJ
Zhou
Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology.|Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai, People's Republic of China.
Kai-Kai
KK
Chang
Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology.
Hui-Li
HL
Yang
Clinical and Translational Research CenterShanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Li-Ping
LP
Jin
Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, mqli@fudan.edu.cn zhuxiaoyong@fudan.edu.cn.|Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai, People's Republic of China.
Xiao-Yong
XY
Zhu
Laboratory for Reproductive ImmunologyHospital of Obstetrics and Gynecology, mqli@fudan.edu.cn zhuxiaoyong@fudan.edu.cn.|Key Laboratory of Reproduction Regulation of NPFPCSIPPR, IRD, Fudan University, Shanghai, People's Republic of China.|Shanghai Key Laboratory of Female Reproductive Endocrine Related DiseasesShanghai, People's Republic of China.
Ming-Qing
MQ
Li
D000328:Adult; D002465:Cell Movement; D049109:Cell Proliferation; D018920:Coculture Techniques; D004715:Endometriosis / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007378:Interleukins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult; D000099180:Interleukin-24
D007378:Interleukins; D000099180:Interleukin-24