[논문]Inhibition of Interleukin-12 Production in Mouse Macrophages via Decreased Nuclear <tex>$Factor-\\kappaB$</tex> DNA Binding Activity by Myricetin, a Naturally Occurring Flavonoid

Kang Bok Yun; Kim Seung Hyun; Cho Dae Ho; Kim Tae Sung

doi:10.1007/bf02977791

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

Archives of pharmacal research : a publication of the Pharmaceutical Society of Korea, v.28 no.3, 2005년, pp.274 - 279

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)

Abstract ▼ AI-Helper

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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제안 방법

In particular, deleting the sequences to -185 (p40/185) did not 시minish the LPS-dependent promoter activity and the inhibitory effect of myricetin was still observed, suggesting that the target site for myricetin resides within this region. To dire거ly test the role of a NF kB site found between 너 21 and 너 31 of the p40 promoter in the myricetin-mediated inhibitory actions, a linker scanning m니tation was introd니ced into the NF-kB site within the context of the -689/+98 construct (p40/LS). LPS-dependent promoter activation was still observed with p40/LS, although significantly red니ced, consistent with the previo니s findings in which the NF-kB site was shown to be important for the LPS-mediated ind니ction of the p40 promoter.

대상 데이터

Spleen cell populations and macrophages from mice were maintained in Dulbecco's modified Eagle's medium (DMEM) containing 10% fetal bovine serum and antibiotics. The LPS (from E. coli 0111:B4) and myricetin were purchased from Sigma-Aldrich Chemical Co. (St. Louis, MO, USA). A 10 mg/mL stock s이니tion of myricetin was prepared by diss이ving in ethanol, and diluted kito the medium, at least 400-fold, such that the final concentra tion of the solvent had no effect on cell growth and on IL-12 p「od니Gtion.

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DOI : 10.1007/BF02977791 [무료]
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