The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Inhibition of ERK1/2 by silymarin in mouse mesangial cells

  • Youn, Cha Kyung (Department of Premedical Sciences, Chosun University College of Medicine) ;
  • Cho, Sung Il (Department of Otolaryngology-Head and Neck Surgery, Chosun University College of Medicine) ;
  • Lee, Min Young (Department of Pharmacology, Chosun University College of Medicine) ;
  • Jeon, Young Jin (Department of Pharmacology, Chosun University College of Medicine) ;
  • Lee, Seog Ki (Department of Thoracic and Cardiovascular Surgery, Chosun University College of Medicine)
  • Received : 2016.10.17
  • Accepted : 2016.11.14
  • Published : 2017.01.01
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Abstract

The present study aimed to show that pro-inflammatory cytokines [tumor necrosis factor (TNF)-${\alpha}$, interferon (IFN)-${\gamma}$, and interleukin (IL)-$1{\beta}$] 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-${\alpha}$; 5 ng/ml, IFN-${\gamma}$; 5 ng/ml, and IL-$1{\beta}$; 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-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$)-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.

Keywords

References

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