Involvement of nuclear factor-kappaB in the inhibition of interleukin-12 production from mouse macrophages by baicalein, a flavonoid in Scutellaria baicalensis.
Involvement of nuclear factor-kappaB in the inhibition of interleukin-12 production from mouse macrophages by baicalein, a flavonoid in Scutellaria baicalensis.
复制标题
黄芩素（黄芩中的一种黄酮类化合物）参与核因子-κB 抑制小鼠巨噬细胞产生白细胞介素 12 的过程。
作者：
B. Kang;S. Chung;S. Kim;D. Cho;T. S. Kim
药理学抑制白细胞介素-12（IL-12）的产生可能是一种治疗策略，用于预防自身免疫实验模型中疾病的发展和进展。在这项研究中，我们研究了黄芩素，一种黄酮类化合物存在于黄芩的根，从脂多糖（LPS）刺激的小鼠巨噬细胞产生IL-12的影响。黄芩素以剂量依赖性方式有效抑制LPS诱导的原代巨噬细胞和RAW264.7单核细胞系产生IL-12（IC 50值分别为43.7和17.4 μ M）。用IL-12基因启动子/荧光素酶构建体转染RAW264.7细胞，观察黄芩素对IL-12基因启动子激活的影响。抑制作用定位于IL-12基因启动子中含有NF-κ B结合位点的区域。此外，LPS激活的巨噬细胞导致与NF-κ B位点的结合活性显著增强，而加入黄芩素后该结合活性显著降低，表明黄芩素通过抑制NF-κ B结合活性来抑制LPS激活的巨噬细胞中IL-12的产生。
Pharmacological inhibition of interleukin-12 (IL-12) production may be a therapeutic strategy for preventing development and progression of disease in experimental models of autoimmunity. In this study we investigated the effects of baicalein, a flavonoid present in the root of Scutellaria baicalensis, on the production of IL-12 from mouse macrophages stimulated with lipopolysaccharide (LPS). Baicalein potently inhibited the LPS-induced IL-12 production from both primary macrophages and RAW264.7 monocytic cell-line in a dose-dependent manner (the IC50 values were 43.7 and 17.4 microM, respectively). The effect of baicalein on IL-12 gene promoter activation was analyzed by transfecting RAW264.7 cells with IL-12 gene promoter/luciferase constructs. The repressive effect mapped to a region in the IL-12 gene promoter containing a binding site for NF-kappaB. Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity to the NF-kappaB site, which significantly decreased upon addition of baicalein, indicating that baicalein inhibited IL-12 production in LPS-activated macrophages via inhibition of NF-kappaB binding activity.