期刊
BMC IMMUNOLOGY
卷 22, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12865-021-00438-4
关键词
Rev-erb alpha; Decidual macrophages; M1/M2 polarization; Pregnancy
类别
资金
- National Key R&D Program of China [2017YFC1001403]
- National Natural Science Foundation of China [31970859, 81630036, 91542116, 81871170]
- Strategic Collaborative Research Program of the Ferring Institute of Reproductive Medicine - Ferring Pharmaceuticals
- Chinese Academy of Sciences [FIRMX200504]
- Shanghai Sailing Program [19YF1404100]
- Program of Shanghai Academic/Technology Research Leader [17XD1400900]
- Innovation-oriented Science and Technology Grant from NHC Key Laboratory of Reproduction Regulation [CX2017-2]
- Innovative research team of highlevel local universities in Shanghai
This study demonstrated that pharmacological activation of Rev-erb alpha using SR9009 could reduce inflammation-induced M1 polarization of macrophages, protect pregnancy, and offer a potential therapeutic strategy for inflammation-induced miscarriage.
Background: Circadian rhythm is an important player for reproduction. Rev-erb alpha, 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-erb alpha. SR9009, an agonist of Rev-erb alpha, may reduce lipopolysaccharide (LPS)-induced M1 polarization of macrophages via activation of PI3K but not NF-kappa B 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-erb alpha 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.
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