G protein-coupled estrogen receptor is involved in the anti-inflammatory effects of genistein in microglia

被引：50

作者：

Du, Zhong-Rui ^{[1
]}

Feng, Xiao-Qing ^{[1
]}

Li, Na ^{[1
]}

Qu, Jiang-Xue ^{[1
]}

Feng, Lu ^{[1
]}

Chen, Lei ^{[1
]}

Chen, Wen-Fang ^{[1
]}

机构：

[1] Qingdao Univ, Shandong Prov Key Lab Pathogenesis & Prevent Neur, Shandong Prov Collaborat Innovat Ctr Neurodegener, Dept Physiol,State Key Disciplines Physiol,Med Co, Qingdao 266071, Peoples R China

来源：

PHYTOMEDICINE | 2018年 / 43卷

基金：

中国国家自然科学基金;

关键词：

Genistein; Microglia; G protein-coupled estrogen receptor; Lipopolysaccharide; Neuroinflammation; NF-KAPPA-B; PARKINSONS-DISEASE; SIGNALING PATHWAYS; GENE-EXPRESSION; UP-REGULATION; CELLS; INFLAMMATION; ACTIVATION; GPR30; TLR4;

D O I：

10.1016/j.phymed.2018.03.039

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Background: Genistein (GEN), a phytoestrogen that is extracted from leguminous plants, can bind to estrogen receptor and exert biological effects. G protein-coupled estrogen receptor (GPER), a novel membrane estrogen receptor, has been reported to be involved in the anti-inflammatory process. In the present study, using BV2 microglial cell line and primary microglial culture, we evaluated the involvement of GPER in the anti-inflammatory effects of genistein against lipopolysaccharide (LPS)-induced microglia activation. Methods: The anti-inflammatory effects of genistein were investigated in LPS-induced microglial activation in murine BV2 microglial cell line and primary microglial culture. Anti-inflammatory properties of genistein were determined by MTT, real time PCR, ELISA and western blot analysis. The pharmacological blockade and lentivirus-mediated siRNA knockdown of GPER were used to study the underlying mechanism. Results: The results showed that genistein exerted inhibitory effects on LPS-induced expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6). Pre-treatment with GPER antagonist G15 could significantly block the anti-inflammatory effects of genistein. Moreover, the inhibitory effects of genistein on LPS-induced activation of MAPKs and NF-kappa B signaling pathways could also be blocked by G15. Lentivirus-mediated siRNA knockdown of GPER significantly inhibited the anti-inflammatory effects of genistein in BV2 cells. Further study revealed that genistein treatment could increase the gene and protein expressions of GPER in BV2 cells. Conclusion: Taken together, these data provide the first evidence that genistein exerts anti-inflammatory effects in microglial cells via GPER activation. These beneficial effects of genistein may represent a new strategy for the treatment of neuroinflammatory diseases.

引用

页码：11 / 20

页数：10

共 37 条

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