IL-25 promotes trophoblast proliferation and invasion via binding with IL-17RB and associated with PE

ABSTRACT

Introduction: Interleukin-25 is a Th2 interleukin and has been shown to influence cell behavior. This study aims to illustrate its affection on extravillous trophoblasts function and association with PE. Methods qPCR and immunohistochemistry demonstrate IL-25 and IL-17RB expression. CCK-8 test and transwell were to access the behavior of HTR8 in the presence or absence of IL-25, IL-25 neutralization antibody. Results EVTs and HTR8 express IL-25 and IL-17RB. IL-25 promotes proliferation and invasion (p< 0.05),which was abolished in the presence of IL-25Ab (p< 0.05). Conclusion: IL-25 may contribute to promote trophoblast invasion and proliferation and abnormal decline of IL-25 might be associated with PE.

Methods: qPCR and immunohistochemistry (IHC) were used to demonstrate IL-25 and its receptor IL-17RB expression in primary human trophoblasts of normal first- and third- trimester, as well as third-trimester of PE. CCK-8 test and transwell invasion system in vitro were applied separately to access the behavior of trophoblast cell line (HTR8) in the presence or absence of IL-25, IL-25 neutralization antibody (IL-25 Ab).

Results: EVTs and HTR8 express IL-25 and IL-17RB. The expressions increase in third-trimester during normal pregnancy. In PE, both of IL-25 and IL-17RB expressions decrease (p< 0.05). IL-25 for 24 h promoted HTR8 proliferation and invasion (p< 0.05). The effect was abolished in the presence of IL-25Ab (p< 0.05).

Conclusion: This study demonstrates that IL-25 may contribute to promote trophoblast invasion and proliferation and abnormal decline of IL-25 might be associated with PE.

KEYWORDS:

• IL-25/trophoblast/proliferation/ invasion/ pre-eclampsia

Acknowledgments

This program was supported by the Shanghai Key Program of Clinical Science and Technology Innovation (17411950500; 17411950501; 18511105602), National Science Foundation of China (81741047; 81971411), Shanghai Medical Center of Key Programs for Female Reproductive Diseases (2017ZZ01016), National Key Basic Research Plan of China (973 Plan) (2015CB943300), and The Major Program of the National 13^th Five-Year Plan of China (2016YFC1000400).

Disclosure statement

No potential conflict of interest was reported by the authors.

Author Contributions

Siyu Liu conceived ideas for the project, performed the experiments, analysed data and wrote the paper. Yi Sun contributed ideas for the project and experimental data. Yao Tang, Rong Hu, Qiongjie Zhou and Xiaotian Li critically reviewed the paper. Xiaotian Li conceived ideas for the project, contributed to experimental design, coordinated the study and edited the manuscript. All authors reviewed the results and approved the final version of the manuscript.

Additional information

Funding

This work was supported by the The Major Program of the National 13th Five‐Year Plan of China [2016YFC1000400]; Shanghai Medical Center of Key Programs for Female Reproductive Diseases [2017ZZ01016]; Shanghai Key Program of Clinical Science and Technology Innovation [17411950500; 17411950501; 18511105602]; National Natural Science Foundation of China [81741047; 81971411]; National Key Basic Research Plan of China (973 Plan) [2015CB943300].