Estrogen-induced nongenomic calcium signaling inhibits lipopolysaccharide-stimulated tumor necrosis factor α production in macrophages.

Estrogen is traditionally thought to exert genomic actions through members of the nuclear receptor family. Here, we investigated the rapid nongenomic effects of 17β-estradiol (E2) on tumor necrosis factor α (TNF-α) production following lipopolysaccharide (LPS) stimulation in mouse bone marrow-derive...

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Autores principales:	Limin Liu, Ying Zhao, Keming Xie, Xiaodong Sun, Yuzhen Gao, Zufeng Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7f4102d8f8eb444bb1e8d9b8e9639708
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spelling	oai:doaj.org-article:7f4102d8f8eb444bb1e8d9b8e96397082021-11-18T08:40:39ZEstrogen-induced nongenomic calcium signaling inhibits lipopolysaccharide-stimulated tumor necrosis factor α production in macrophages.1932-620310.1371/journal.pone.0083072https://doaj.org/article/7f4102d8f8eb444bb1e8d9b8e96397082013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24376635/?tool=EBIhttps://doaj.org/toc/1932-6203Estrogen is traditionally thought to exert genomic actions through members of the nuclear receptor family. Here, we investigated the rapid nongenomic effects of 17β-estradiol (E2) on tumor necrosis factor α (TNF-α) production following lipopolysaccharide (LPS) stimulation in mouse bone marrow-derived macrophages (BMMs). We found that LPS induced TNF-α production in BMMs via phosphorylation of p38 mitogen-activated protein kinase (MAPK). E2 itself did not affect the MAPK pathway, although it attenuated LPS-induced TNF-α production through suppression of p38 MAPK activation. Recently, G protein-coupled receptor 30 (GPR30) was suggested to be a membrane estrogen receptor (mER) that can mediate nongenomic estradiol signaling. We found that BMMs expressed both intracellular estrogen receptors (iER) and mER GPR30. The specific GPR30 antagonist G-15 significantly blocked effects of estradiol on LPS-induced TNF-α production, whereas an iER antagonist did not. Moreover, E2 induced a rapid rise in intracellular free Ca(2+) that was due to the influx of extracellular Ca(2+) and was not inhibited by an iER antagonist or silencing of iER. Ca(2+) influx was also induced by an impermeable E2 conjugated to BSA (E2-BSA), which has been used to investigate the nongenomic effects of estrogen. Consequently, Ca(2+), a pivotal factor in E2-stimulated nongenomic action, was identified as the key mediator. The inhibitory effects of E2 on LPS-induced TNF-α production and p38 MAPK phosphorylation were dependent on E2-triggered Ca(2+) influx because BAPTA, an intracellular Ca(2+) chelator, prevented these effects. Taken together, these data indicate that E2 can down-regulate LPS-induced TNF-α production via blockade of p38 MAPK phosphorylation through the mER-mediated nongenomic Ca(2+) signaling pathway in BMMs.Limin LiuYing ZhaoKeming XieXiaodong SunYuzhen GaoZufeng WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e83072 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Limin Liu Ying Zhao Keming Xie Xiaodong Sun Yuzhen Gao Zufeng Wang Estrogen-induced nongenomic calcium signaling inhibits lipopolysaccharide-stimulated tumor necrosis factor α production in macrophages.
description	Estrogen is traditionally thought to exert genomic actions through members of the nuclear receptor family. Here, we investigated the rapid nongenomic effects of 17β-estradiol (E2) on tumor necrosis factor α (TNF-α) production following lipopolysaccharide (LPS) stimulation in mouse bone marrow-derived macrophages (BMMs). We found that LPS induced TNF-α production in BMMs via phosphorylation of p38 mitogen-activated protein kinase (MAPK). E2 itself did not affect the MAPK pathway, although it attenuated LPS-induced TNF-α production through suppression of p38 MAPK activation. Recently, G protein-coupled receptor 30 (GPR30) was suggested to be a membrane estrogen receptor (mER) that can mediate nongenomic estradiol signaling. We found that BMMs expressed both intracellular estrogen receptors (iER) and mER GPR30. The specific GPR30 antagonist G-15 significantly blocked effects of estradiol on LPS-induced TNF-α production, whereas an iER antagonist did not. Moreover, E2 induced a rapid rise in intracellular free Ca(2+) that was due to the influx of extracellular Ca(2+) and was not inhibited by an iER antagonist or silencing of iER. Ca(2+) influx was also induced by an impermeable E2 conjugated to BSA (E2-BSA), which has been used to investigate the nongenomic effects of estrogen. Consequently, Ca(2+), a pivotal factor in E2-stimulated nongenomic action, was identified as the key mediator. The inhibitory effects of E2 on LPS-induced TNF-α production and p38 MAPK phosphorylation were dependent on E2-triggered Ca(2+) influx because BAPTA, an intracellular Ca(2+) chelator, prevented these effects. Taken together, these data indicate that E2 can down-regulate LPS-induced TNF-α production via blockade of p38 MAPK phosphorylation through the mER-mediated nongenomic Ca(2+) signaling pathway in BMMs.
format	article
author	Limin Liu Ying Zhao Keming Xie Xiaodong Sun Yuzhen Gao Zufeng Wang
author_facet	Limin Liu Ying Zhao Keming Xie Xiaodong Sun Yuzhen Gao Zufeng Wang
author_sort	Limin Liu
title	Estrogen-induced nongenomic calcium signaling inhibits lipopolysaccharide-stimulated tumor necrosis factor α production in macrophages.
title_short	Estrogen-induced nongenomic calcium signaling inhibits lipopolysaccharide-stimulated tumor necrosis factor α production in macrophages.
title_full	Estrogen-induced nongenomic calcium signaling inhibits lipopolysaccharide-stimulated tumor necrosis factor α production in macrophages.
title_fullStr	Estrogen-induced nongenomic calcium signaling inhibits lipopolysaccharide-stimulated tumor necrosis factor α production in macrophages.
title_full_unstemmed	Estrogen-induced nongenomic calcium signaling inhibits lipopolysaccharide-stimulated tumor necrosis factor α production in macrophages.
title_sort	estrogen-induced nongenomic calcium signaling inhibits lipopolysaccharide-stimulated tumor necrosis factor α production in macrophages.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/7f4102d8f8eb444bb1e8d9b8e9639708
work_keys_str_mv	AT liminliu estrogeninducednongenomiccalciumsignalinginhibitslipopolysaccharidestimulatedtumornecrosisfactoraproductioninmacrophages AT yingzhao estrogeninducednongenomiccalciumsignalinginhibitslipopolysaccharidestimulatedtumornecrosisfactoraproductioninmacrophages AT kemingxie estrogeninducednongenomiccalciumsignalinginhibitslipopolysaccharidestimulatedtumornecrosisfactoraproductioninmacrophages AT xiaodongsun estrogeninducednongenomiccalciumsignalinginhibitslipopolysaccharidestimulatedtumornecrosisfactoraproductioninmacrophages AT yuzhengao estrogeninducednongenomiccalciumsignalinginhibitslipopolysaccharidestimulatedtumornecrosisfactoraproductioninmacrophages AT zufengwang estrogeninducednongenomiccalciumsignalinginhibitslipopolysaccharidestimulatedtumornecrosisfactoraproductioninmacrophages
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Estrogen-induced nongenomic calcium signaling inhibits lipopolysaccharide-stimulated tumor necrosis factor α production in macrophages.

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