KMID : 0811720170210010117
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Korean Journal of Physiology & Pharmacology 2017 Volume.21 No. 1 p.117 ~ p.124
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Inhibition of ERK1/2 by silymarin in mouse mesangial cells
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Youn Cha-Kyung
Cho Sung-Il Lee Min-Young Jeon Young-Jin Lee Seog-Ki
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Abstract
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The present study aimed to show that pro-inflammatory cytokines [tumor necrosis factor (TNF)-¥á, interferon (IFN)-¥ã, and interleukin (IL)-1¥â] 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-¥á; 5 ng/ml, IFN-¥ã; 5 ng/ml, and IL-1¥â; 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 (Silybum marianum), attenuates cytokine mixture (TNF-¥á, IFN-¥ã, and IL-1¥â)-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.
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KEYWORD
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Cytokine, ERK1/2, iNOS, Mesangial cells, Nitric oxide
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