Estrogen receptor-independent inhibition of tumor necrosis factor-α gene expression by phytoestrogen equol is mediated by blocking nuclear factor-κB activation in mouse macrophages

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Title
Estrogen receptor-independent inhibition of tumor necrosis factor-α gene expression by phytoestrogen equol is mediated by blocking nuclear factor-κB activation in mouse macrophages
Author(s)
Jong Soon KangYeo Dae Yoon; Mi Hwa Han; Sang Bae Han; Kiho Lee; Moo Rim Kang; Eun Yi Moon; Y J Jeon; Song Kyu Park; Hwan Mook Kim
Bibliographic Citation
Biochemical Pharmacology, vol. 71, no. 1, pp. 136-143
Publication Year
2005
Abstract
Equol has been suggested to possess protective effects on bone. However, the underlying mechanism of osteoprotective effect of equol has not been fully understood. In the present study, we examined the effect of equol on tumor necrosis factor-α (TNF-α) gene expression to elucidate a possible mechanism by which equol exerts osteoprotective effect. In vivo administration of equol inhibited TNF-α production by peritoneal macrophages isolated from LPS-treated mice. Equol also dose-dependently inhibited TNF-α production and TNF-α mRNA expression in LPS-stimulated mouse macrophages. Pretreatment of cells with ICI 182.780, an estrogen receptor antagonist, had no effect on the inhibitory efficacy of equol on LPS-induced TNF-α production. Further study demonstrated that equol inhibited NF-κB DNA binding and NF-κB-dependent reporter gene expression in activated RAW 264.7 cells. Moreover, equol blocked degradation of IκBα and IκBβ and nuclear translocation of p65 subunit of NF-κB in activated RAW 264.7 cells. These results suggest that the inhibitory effect of equol on TNF-α expression is mediated, at least in part, by blocking NF-κB activation and the inhibition of TNF-α expression by equol might be involved in its osteoprotective effect.
Keyword
EquolOsteoporosisTNF-αNF-κB
ISSN
0006-2952
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bcp.2005.10.009
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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