Activation of Rev-erbα attenuates lipopolysaccharide-induced inflammatory reactions in human endometrial stroma cells via suppressing TLR4-regulated NF-κB activation. (14th August 2019)

• Record Type: Journal Article
• Authors: Zhao, Weijie; Cui, Liyuan; Huang, Xixi; Wang, Songcun; Li, Dajin; Li, Liping; Sun, Yan; Du, Meirong
• Is Part Of: Acta biochimica et biophysica Sinica. Volume 51:Number 9(2019)
• Page Start: 908
• Page End: 914
• Publication Date: 2019-08-14
• Subjects: Rev-erbα -- human endometrial stroma cells -- LPS -- inflammation; Biochemistry -- Periodicals; Biophysics -- Periodicals; 572.05
• DOI: 10.1093/abbs/gmz078
• Languages: English
• ISSNs: 1672-9145

Abstract

Abstract: Perturbation of the circadian rhythm damages the biological characteristics of cells and leads to their dysfunction. Rev-erbα, an important gene in the transcription-translation loop of circadian rhythm, is involved in regulating the balance between pro-inflammation and anti-inflammation. The disruption of this balance in human endometrial stroma cells (hESCs) destroys their biological behavior function in maintaining the menstrual cycle and embryonic implantation. Whether pharmacological modulation of Rev-erbα affects the inflammation of hESCs remains unclear. In this study, we treated hESCs with lipopolysaccharide (LPS) and found that LPS treatment increased the mRNA levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, IL-18, and TNFα, and the secretion of IL-6. SR9009, a Rev-erbα agonist, significantly alleviated the LPS-induced production of pro-inflammatory cytokines in hESCs. Meanwhile, knockdown of Rev-erbα increased the expressions of IL-1β, IL-6, and IL-8, accompanied by an increased mRNA level of the core clock gene Bmal1 . Western blot analysis showed that SR9009 inhibited the expression of toll-like receptor 4 (TLR4) and the activation of NF-κB induced by LPS. All these findings suggested that pharmacological activation of Rev-erbα attenuated the LPS-induced inflammatory response of hESCs by suppressing TLR4-regulated NF-κB activation. This study may provide a strategy for preventing inflammation-related endometrial dysfunction and infertility or recurrent implantation failure.