Youn Cha Kyung, Cho Sung Il, Lee Min Young, Jeon Young Jin, Lee Seog Ki
Department of Premedical Sciences, Chosun University College of Medicine, Gwangju 61452, Korea.
Department of Otolaryngology-Head and Neck Surgery, Chosun University College of Medicine, Gwangju 61452, Korea.
Korean J Physiol Pharmacol. 2017 Jan;21(1):117-124. doi: 10.4196/kjpp.2017.21.1.117. Epub 2016 Dec 21.
The present study aimed to show that pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-1β] synergistically induce the production of nitric oxide (NO) production in mouse mesangial cells, which play an important role in inflammatory glomerular injury. We also found that co-treatment with cytokines at low doses (TNF-α; 5 ng/ml, IFN-γ; 5 ng/ml, and IL-1β; 1.25 U/ml) synergistically induced NO production, whereas treatment with each cytokine alone did not increase NO production at doses up to 100 ng/ml or 50 U/ml. Silymarin, a polyphenolic flavonoid isolated from milk thistle (), attenuates cytokine mixture (TNF-α, IFN-γ, and IL-1β)-induced NO production. Western blot and RT-PCR analyses showed that silymarin inhibits inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Silymarin also inhibited extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) phosphorylation. Collectively, we have demonstrated that silymarin inhibits NO production in mouse mesangial cells, and may act as a useful anti-inflammatory agent.
本研究旨在表明促炎细胞因子[肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ和白细胞介素（IL）-1β]在小鼠系膜细胞中协同诱导一氧化氮（NO）的产生，而系膜细胞在炎症性肾小球损伤中起重要作用。我们还发现，低剂量细胞因子（TNF-α；5 ng/ml、IFN-γ；5 ng/ml和IL-1β；1.25 U/ml）联合处理可协同诱导NO产生，而单独使用每种细胞因子在高达100 ng/ml或50 U/ml的剂量下均不会增加NO产生。水飞蓟宾是从水飞蓟中分离出的一种多酚类黄酮，可减弱细胞因子混合物（TNF-α、IFN-γ和IL-1β）诱导的NO产生。蛋白质印迹和逆转录-聚合酶链反应分析表明，水飞蓟宾以剂量依赖的方式抑制诱导型一氧化氮合酶（iNOS）的表达。水飞蓟宾还抑制细胞外信号调节蛋白激酶-1和-2（ERK1/2）的磷酸化。总体而言，我们证明了水飞蓟宾可抑制小鼠系膜细胞中NO的产生，并可能作为一种有用的抗炎剂。
