GPER negatively regulates TNFα-induced IL-6 production in human breast cancer cells <i>via</i> NF-κB pathway
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- Okamoto Mariko
- Laboratory of Veterinary Immunology, School of Veterinary Medicine, Azabu University, Sagamihara 252-5201, Japan
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- Mizukami Yoichi
- Center for Gene Research, Yamaguchi University, Ube 755-8505, Japan
書誌事項
- タイトル別名
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- GPER negatively regulates TNFα-induced IL-6 production in human breast cancer cells <i>via</i> NF-κB pathway
抄録
Estrogen is known to have anti-inflammatory effects, that are thought to be mediated by the classical estrogen receptors (ERs), ERα and ERβ. G protein coupled estrogen receptor1 (GPER) is a novel membrane-type estrogen receptor that can mediate non-genomic estrogenic responses. Although there have been several reports asserting that the participation of GPER in anti-inflammatory effects is induced by estrogen, the role of GPER remains poorly understood. In this study, we investigated the involvement of GPER in the regulation of a representative inflammatory cytokine, IL-6. We first examined the expression of IL-6 mRNA by TNFα stimulation in the transfection of GPER-expression plasmid into HeLa cells. Exogenous GPER significantly inhibited TNFα-induced IL-6 expression, and blocked NF-κB promoter activity inducing the expression of IL-6 in a dose-dependent manner. The promoter activity was restored almost to control level by transfection with the C-terminal deletion mutant of GPER. Similar results have been observed in endogenous GPER using SKBR3 cells which do not express the classical ERs. The data have been validated by treatment of GPER with siRNA. These findings indicate that GPER negatively regulates TNFα-induced IL-6 expression, probably through inhibition of NF-κB promoter activity by a signal(s) derived from the C-terminal region of GPER.
収録刊行物
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- Endocrine Journal
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Endocrine Journal 63 (5), 485-493, 2016
一般社団法人 日本内分泌学会
