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Inhibition of Interleukin-12 Production in Mouse Macrophages via Decreased Nuclear $Factor-\kappaB$ DNA Binding Activity by Myricetin, a Naturally Occurring Flavonoid  

Kang Bok Yun (College of Pharmacy and Research Institute of Drug Development, Chonnam National University)
Kim Seung Hyun (College of Pharmacy and Research Institute of Drug Development, Chonnam National University)
Cho Dae Ho (Department of Life Science, Sookmyung Womens University)
Kim Tae Sung (College of Pharmacy and Research Institute of Drug Development, Chonnam National University)
Publication Information
Archives of Pharmacal Research / v.28, no.3, 2005 , pp. 274-279 More about this Journal
Abstract
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 cell-line 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-${\kappa}B$. Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity to the NF-${\kappa}B$ site, which significantly decreased upon addition of myricetin, indicating that myricetin inhibited IL-12 production in LPS-activated macrophages via the down­regulation of NF-KB binding activity.
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