Ginsenoside Rg5:Rk1 attenuates TNF-α/IFN-γ-induced production of thymus- and activation-regulated chemokine (TARC/CCL17) and LPS-induced NO production via downregulation of NF-κB/p38 MAPK/STAT1 signaling in human keratinocytes and macrophages
Ginsenoside Rg5:Rk1 attenuates TNF-α/IFN-γ-induced production of thymus- and activation-regulated chemokine (TARC/CCL17) and LPS-induced NO production via downregulation of NF-κB/p38 MAPK/STAT1 signaling in human keratinocytes and macrophages
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DOI：
10.1007/s11626-015-9983-y
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发表时间：
2016-03-01
影响因子：
2.1
通讯作者：
Yang, Deok-Chun
中科院分区：
文献类型：
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作者：
Ahn, Sungeun;Siddiqi, Muhammad Hanif;Yang, Deok-Chun
特应性皮炎(AD)是一种慢性皮肤病，影响着全球数百万人。角质形成细胞和巨噬细胞是AD发生发展中起关键作用的两种细胞类型。这些细胞产生不同的趋化因子和细胞因子，尤其是胸腺和活化调节趋化因子(TARC/CCL17)和巨噬细胞衍生趋化因子(MDC/CCL22)，以及通过诱导型一氧化氮合酶(INOS)和COX2产生的一氧化氮(NO)。这些介质被认为是AD发病机制的重要调节因子。虽然已经研究了几种治疗AD的天然化合物，但人参Rg5：Rk1对AD的影响尚未见报道。在本研究中，我们评价了Rg5：RK1对肿瘤坏死因子-α/干扰素-γ刺激的角质形成细胞(HaCaT细胞)和内毒素刺激的巨噬细胞(RAW 264.7细胞)的抑制作用。酶联免疫吸附试验(ELISA)结果显示，Rg5：Rk1处理HaCaT细胞后，可显著降低肿瘤坏死因子-α/干扰素-γ诱导的TARC/CCL17表达的增加，并呈剂量依赖关系。此外，RG5：RK1还可减少RAW 264.7细胞内毒素介导的一氧化氮(NO)和活性氧(ROS)的产生。上述AD介质的信使RNA(MRNAs)表达也显著降低。Rg5：Rk1可减弱肿瘤坏死因子-α/干扰素-γ诱导的HaCaT细胞p38MAPK、STAT1和NF-kappa B/ikkβ的磷酸化。综上所述，这些发现提示人参皂苷Rg5：Rk1可能通过抑制NF-kappaB/p38MAPK/STAT1信号通路而具有潜在的抗AD作用。
Atopic dermatitis (AD) is a chronic skin disease that affects millions of people worldwide. Keratinocytes and macrophages are two cells types that play a pivotal role in the development of AD. These cells produced different chemokines and cytokines, especially thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), as well as nitric oxide (NO) through inducible nitric oxide synthase (iNOS) and COX2 in response to stimulation by TNF-alpha/IFN-gamma and lipopolysaccharide (LPS) respectively. These mediators are thought to be crucial regulators of the pathogenesis of AD. Although several natural compounds to treat AD have been studied, the effect of Rg5:Rk1 from Panax ginseng (P.ginseng) on AD has not yet been investigated. In this study, we evaluated the inhibitory effect of Rg5: Rk1 on TNF-alpha/IFN-gamma stimulated keratinocytes (HaCaT cells) and LPS-stimulated macrophages (RAW 264.7 cells). Enzyme-linked immunosorbent assay (ELISA) data showed that pretreatment of HaCaT cells with Rg5: Rk1 significantly reduced the TNF-alpha/IFN-gamma-induced increase in TARC/CCL17 expression in a dose-dependent manner. In addition, Rg5: Rk1 decreased LPS-mediated nitric oxide (NO) and reactive oxygen species (ROS) production in RAW 264.7 cells. A considerable reduction in messenger RNA (mRNA) expression of the aforementioned AD mediators was also observed. Pretreatment with Rg5: Rk1 attenuated the TNF-alpha/IFN-gamma-induced phosphorylation of p38MAPK, STAT1, and NF-kappa B/IKK beta in HaCaT cells. Together, these findings suggest that ginsenoside Rg5: Rk1 may have a potential anti-AD effect by suppressing NF-kappa B/p38 MAPK/STAT1 signaling.