NLRC5 Inhibits Inflammation of Secretory Phase Ectopic Endometrial Stromal Cells by Up-Regulating Autophagy in Ovarian Endometriosis.

Runhua He,Xiaojing Liu,Lei Zhan,Jing Zhang,Yunxia Cao,Liutao Fu,Zhongzheng Wang,Wenyan Wang,Lijun Shui,Shiying Sun,Yijun Fan

doi:10.3389/fphar.2020.01281

Abstract

Nod-like receptor (NLR) family caspase activation and recruitment domain containing 5 (NLRC5) is a newly identified sub-class of the NLR family. It regulates inflammation and has a key function in innate and adaptive immunologic reactions. Autophagy has been reported to be crucially linked to the pathogenesis of endometriosis. Our recent study identify there is a negative correlation between NLRC5 and autophagy in endometriosis, indicating that NLRC5 and autophagy together act as promising predictors in endometriosis patients. However, the mechanism associating NLRC5 and autophagy in endometriosis is still not completely understood. We hypothesize that autophagy could be involved in NLRC5-mediated inflammation in endometriosis. In order to validate the assumption, we evaluate the effects of NLRC5 and autophagy in the inflammation of ectopic endometrial stromal cells (EESCs) of ovarian endometriosis patients, to specifically determine whether autophagy is involved in NLRC5-mediated inflammation in EESCs. Our results show that over-expression of NLRC5 results in the up-regulation of autophagy in EESCs and inhibition of NLRC5 restricts the level of autophagy in EESCs. Furthermore, over-expression of NLRC5 and promotion of autophagy inhibit interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expressions, whereas inhibition of NLRC5 and autophagy up-regulate IL-6 and TNF-α expressions in EESCs. Additionally, promotion of autophagy contributes to the NLRC5-mediated inhibition of IL-6 and TNF-α expressions in EESCs; inhibition of autophagy restricts NLRC5-mediated inhibition of IL-6 and TNF-α expressions in EESCs. Our results suggest that over-expression of NLRC5 promotes autophagy, thereby inhibiting inflammation in ovarian endometriosis.

Highlights

Endometriosis is a benign gynecologic disorder defined as the ectopic growth of endometrium outside the uterus, on the ovaries, pelvic peritoneum, and rectovaginal septum
Western blotting and Quantitative RealTime PCR (qRT-PCR) were performed to compare the levels of NLRC5 inflammation and autophagy in Endometrial Stromal Cells (ESCs) of patients with endometriosis and ESCs of patients with leiomyoma
Studies propose that NLRC5 plays a key role in inflammation, but the conclusion is controversial

Summary

Introduction

Endometriosis is a benign gynecologic disorder defined as the ectopic growth of endometrium outside the uterus, on the ovaries, pelvic peritoneum, and rectovaginal septum. Endometriosis affects about 10% of women in the reproductive age and is associated with infertility, dysmenorrhea, and chronic pelvic pain (McKinnon et al, 2018; Zhan et al, 2018a). Current treatments for endometriosis include surgery and pharmacotherapy (Ferrero et al, 2015; Ferrero et al, 2018). Recent studies indicate that local inflammatory reaction in the peritoneal environment supports the development or maintenance of endometriosis, and the ectopic endometrial stromal cells (EESCs) are one of the major sources of cytokines (Khan et al, 2013; Takai et al, 2013; Zhan et al, 2018a)

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Results

Conclusion