Estrogen receptor-independent inhibition of tumor necrosis factor-alpha gene expression by phytoestrogen equol is mediated by blocking nuclear factor-kappaB activation in mouse macrophages.
Estrogen receptor-independent inhibition of tumor necrosis factor-alpha gene expression by phytoestrogen equol is mediated by blocking nuclear factor-kappaB activation in mouse macrophages.
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DOI：
10.1016/j.bcp.2005.10.009
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发表时间：
2005-12
影响因子：
5.8
通讯作者：
J. Kang;Y. Yoon;M. Han;S. Han;Kiho Lee;M. Kang;E. Moon;Y. Jeon;Song-Kyu Park;Hwan‐Mook Kim
中科院分区：
文献类型：
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作者：
J. Kang;Y. Yoon;M. Han;S. Han;Kiho Lee;M. Kang;E. Moon;Y. Jeon;Song-Kyu Park;Hwan‐Mook Kim
雌马酚被认为对骨骼具有保护作用。然而，雌马酚的骨保护作用的潜在机制尚未完全了解。在本研究中，我们研究了雌马酚对肿瘤坏死因子-α（TNF-α）基因表达的影响，以阐明雌马酚发挥骨保护作用的可能机制。雌马酚体内给药可抑制从LPS处理小鼠中分离的腹腔巨噬细胞产生TNF-α。雌马酚还剂量依赖性地抑制LPS刺激的小鼠巨噬细胞中TNF-α的产生和TNF-α mRNA的表达。用雌激素受体拮抗剂ICI 182.780预处理细胞，对雌马酚抑制LPS诱导的TNF-α产生的效果没有影响。进一步的研究表明，雌马酚抑制活化的RAW 264.7细胞中NF-κB B DNA结合和NF-κ B依赖的报告基因表达。雌马酚还能抑制活化RAW 264.7细胞中IκBα和IκBβ的降解以及NF-κB p65亚基的核转位。这些结果表明雌马酚对TNF-α表达的抑制作用至少部分是通过阻断NF-κB活化介导的，雌马酚对TNF-α表达的抑制可能与其骨保护作用有关。
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.