2. Academic Validation
  3. Pharmacological activation of rev-erbα suppresses LPS-induced macrophage M1 polarization and prevents pregnancy loss

Pharmacological activation of rev-erbα suppresses LPS-induced macrophage M1 polarization and prevents pregnancy loss

  • BMC Immunol. 2021 Aug 16;22(1):57. doi: 10.1186/s12865-021-00438-4.
Liyuan Cui  # 1 2,  Feng Xu  # 1 2,  Songcun Wang 1 2,  Xinyi Li 1 2,  Haiyan Lin 3,  Yan Ding 4 5 6,  Meirong Du 7 8 9 10
Affiliations

Affiliations

  • 1 NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, 200090, China.
  • 2 Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200090, China.
  • 3 Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
  • 4 NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, 200090, China. ding_yan@fudan.edu.cn.
  • 5 Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200090, China. ding_yan@fudan.edu.cn.
  • 6 Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Fangxie Road 419, Shanghai, 200011, China. ding_yan@fudan.edu.cn.
  • 7 NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, 200090, China. dmrlq1973@sina.cn.
  • 8 Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200090, China. dmrlq1973@sina.cn.
  • 9 Department of Obstetrics and Gynecology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China. dmrlq1973@sina.cn.
  • 10 Laboratory for Reproductive Immunology, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, ZhaoZhou Road 413, Shanghai, 200011, China. dmrlq1973@sina.cn.
  • # Contributed equally.
PMID: 34399700 DOI: 10.1186/s12865-021-00438-4
Abstract

Background: Circadian rhythm is an important player for reproduction. Rev-erbα, a significant clock gene, is involved in regulating cell differentiation, inflammation and metabolism. Macrophage polarization plays crucial roles in immune tolerance at the maternal-fetus interface, which also modulates the initiation and resolution of inflammation. Alteration of macrophage polarization induces adverse pregnancy outcomes such as infertility, recurrent spontaneous abortion and preterm labor.

Results: Decidual macrophages from LPS-induced mice abortion model displayed M1-like bias, accompanied by decreased expression of Rev-erbα. SR9009, an agonist of Rev-erbα, may reduce lipopolysaccharide (LPS)-induced M1 polarization of macrophages via activation of PI3K but not NF-κB signaling pathway. Furthermore, SR9009 could reduce M1-like polarization of decidual macrophages induced by LPS and attenuate LPS-induced resorption rates in mice model.

Conclusions: Both in vivo and in vitro experiments demonstrated that the pharmacological activation of Rev-erbα using SR9009 could attenuate the effect of LPS on macrophage polarization and protect pregnancy. This study may provide a potential therapeutic strategy for miscarriage induced by inflammation.

Keywords

Decidual macrophages; M1/M2 polarization; Pregnancy; Rev-erbα.

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