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.
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-alpha (TNF-alpha) gene expression to elucidate a possible mechanism by which equol exerts osteoprotective effect. In vivo administration of equol inhibited TNF-alpha production by peritoneal macrophages isolated from LPS-treated mice. Equol also dose-dependently inhibited TNF-alpha production and TNF-alpha 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-alpha production. Further study demonstrated that equol inhibited NF-kappaB DNA binding and NF-kappaB-dependent reporter gene expression in activated RAW 264.7 cells. Moreover, equol blocked degradation of IkappaBalpha and IkappaBbeta and nuclear translocation of p65 subunit of NF-kappaB in activated RAW 264.7 cells. These results suggest that the inhibitory effect of equol on TNF-alpha expression is mediated, at least in part, by blocking NF-kappaB activation and the inhibition of TNF-alpha expression by equol might be involved in its osteoprotective effect.
Kang
Jong Soon
JS
Biovaluation Center, Korea Research Institute of Bioscience and Biotechnology, Taejon, Korea.
Yoon
Yeo Dae
YD
Han
Mi Hwa
MH
Han
Sang-Bae
SB
Lee
Kiho
K
Kang
Moo Rim
MR
Moon
Eun-Yi
EY
Jeon
Young Jin
YJ
Park
Song-Kyu
SK
Kim
Hwan Mook
HM
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D060754:Equol; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology*; D007529:Isoflavones / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D021381:Protein Transport; D011960:Receptors, Estrogen / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D017931:DNA Primers; D007529:Isoflavones; D016328:NF-kappa B; D011960:Receptors, Estrogen; D014409:Tumor Necrosis Factor-alpha; D060754:Equol