Park Young Sun, Lee Ji Eun, Park Jong Il, Myung Cheol Hwan, Lim Young-Ho, Park Chae Kyu, Hwang Jae Sung
Department of Genetic Engineering & Graduate School of Biotechnology, Kyung Hee University, Yongin, Republic of Korea.
KGC R&D Headquarters, Daejeon, Republic of Korea.
J Ginseng Res. 2020 Mar;44(2):274-281. doi: 10.1016/j.jgr.2018.12.006. Epub 2018 Dec 24.
Ultraviolet (UV) goes through the epidermis and promotes release of inflammatory cytokines in keratinocytes. Granulocyte-macrophage colony-stimulating factor (GM-CSF), one of the keratinocyte-derived cytokines, regulates proliferation and differentiation of melanocytes. Extracellular signal-regulated kinase (ERK1/2) and protein kinase C (PKC) signaling pathways regulate expression of GM-CSF. Based on these results, we found that ginsenoside Rh3 prevented GM-CSF production and release in UV-B-exposed SP-1 keratinocytes and that this inhibitory effect resulted from the reduction of PKCδ and ERK phosphorylation.
We investigated the mechanism by which ginsenoside Rh3 from inhibited GM-CSF release from UV-B-irradiated keratinocytes.
Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) or UV-B induced release of GM-CSF in the SP-1 keratinocytes. To elucidate whether the change in GM-CSF expression could be related to PKC signaling, the cells were pretreated with H7, an inhibitor of PKC, and irradiated with UV-B. GM-CSF was decreased by H7 in a dose-dependent manner. When we analyzed which ginsenosides repressed GM-CSF expression among 15 ginsenosides, ginsenoside Rh3 showed the largest decline to 40% of GM-CSF expression in enzyme-linked immunosorbent assay. Western blot analysis showed that TPA enhanced the phosphorylation of PKCδ and ERK in the keratinocytes. When we examined the effect of ginsenoside Rh3, we identified that ginsenoside Rh3 inhibited the TPA-induced phosphorylation levels of PKCδ and ERK.
In summary, we found that ginsenoside Rh3 impeded UV-B-induced GM-CSF production through repression of PKCδ and ERK phosphorylation in SP-1 keratinocytes.
紫外线（UV）穿透表皮并促进角质形成细胞中炎性细胞因子的释放。粒细胞-巨噬细胞集落刺激因子（GM-CSF）是角质形成细胞衍生的细胞因子之一，可调节黑素细胞的增殖和分化。细胞外信号调节激酶（ERK1/2）和蛋白激酶C（PKC）信号通路调节GM-CSF的表达。基于这些结果，我们发现人参皂苷Rh3可阻止UV-B照射的SP-1角质形成细胞中GM-CSF的产生和释放，且这种抑制作用是由于PKCδ和ERK磷酸化的减少所致。
我们研究了人参皂苷Rh3抑制UV-B照射的角质形成细胞释放GM-CSF的机制。
用12-O-十四酰佛波醇-13-乙酸酯（TPA）或UV-B处理可诱导SP-1角质形成细胞释放GM-CSF。为了阐明GM-CSF表达的变化是否与PKC信号有关，细胞先用PKC抑制剂H7预处理，然后用UV-B照射。H7以剂量依赖性方式降低了GM-CSF的水平。当我们分析15种人参皂苷中哪种人参皂苷能抑制GM-CSF表达时，在酶联免疫吸附测定中，人参皂苷Rh3对GM-CSF表达的抑制作用最为显著，降至40%。蛋白质印迹分析表明，TPA可增强角质形成细胞中PKCδ和ERK的磷酸化。当我们检测人参皂苷Rh3的作用时，发现人参皂苷Rh3可抑制TPA诱导的PKCδ和ERK的磷酸化水平。
总之，我们发现人参皂苷Rh3通过抑制SP-1角质形成细胞中PKCδ和ERK的磷酸化来阻碍UV-B诱导的GM-CSF的产生。
