title: Inhibition of ERK1/2 by silymarin in mouse mesangial cells.
abstract: 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 (Silybum marianum), 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.
authors.affiliation: Department of Premedical Sciences, Chosun University College of Medicine, Gwangju 61452, Korea.
authors.forename: Cha Kyung
authors.initials: CK
authors.lastname: Youn
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Chosun University College of Medicine, Gwangju 61452, Korea.
authors.forename: Sung Il
authors.initials: SI
authors.lastname: Cho
authors.affiliation: Department of Pharmacology, Chosun University College of Medicine, Gwangju 61452, Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, Chosun University College of Medicine, Gwangju 61452, Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Jeon
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Chosun University College of Medicine, Gwangju 61452, Korea.
authors.forename: Seog Ki
authors.initials: SK
authors.lastname: Lee
keywords: Cytokine; ERK1/2; Mesangial cells; Nitric oxide; iNOS