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KMID : 0043320050280030274
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Archives of Pharmacal Research
2005 Volume.28 No. 3 p.274 ~ p.279
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Inhibition of Interleukin-12 Production in Mouse Macrophagesvia Decreased Nuclear Factor-κB DNA Binding Activity by Myricetin, a Naturally Occurring Flavonoid
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Kang BY
Kim SH/Cho DH/Kim TS
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Abstract
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Pharmacological inhibition of interleukin-12 (IL-12) production may be a therapeutic strategy for preventing the development and progression of disease in experimental models of autoimmunity. In this study, the effects of myricetin, a naturally occurring flavonoid present in fruits, vegetables and medicinal herbs, on the production of IL-12 were investigated in mouse macrophages stimulated with lipopolysaccharide (LPS). Myricetin significantly inhibited the LPSinduced IL-12 production from both primary macrophages and the RAW264.7 monocytic cellline in a dose-dependent manner. The effect of myricetin on IL-12 gene promoter activation was analyzed by transfecting RAW264.7 cells with IL-12 gene promoter/luciferase constructs. The repressive effect was mapped to a region in the IL-12 gene promoter containing a binding site for NF-κB. Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity to the NF-κB site, which significantly decreased upon addition of myricetin, indicating that myricetin inhibited IL-12 production in LPS-activated macrophages via the downregulation of NF-κB binding activity.
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