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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

  • Sungeun Ahn
  • Muhammad Hanif Siddiqi
  • Veronica Castro Aceituno
  • Shakina Yesmin Simu
  • Jinglou Zhang
  • Zuly Elizabeth Jimenez Perez
  • Yu-Jin Kim
  • Deok-Chun Yang
Article

Abstract

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-α/IFN-γ 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-α/IFN-γ 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-α/IFN-γ-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-α/IFN-γ-induced phosphorylation of p38 MAPK, STAT1, and NF-κB/IKKβ in HaCaT cells. Together, these findings suggest that ginsenoside Rg5:Rk1 may have a potential anti-AD effect by suppressing NF-κB/p38 MAPK/STAT1 signaling.

Keywords

Inflammation Atopic dermatitis Keratinocytes/macrophages TARC/CCL17 NF-κB p38 MAPK STAT1 

Notes

Acknowledgments

This research was supported by grants 312064-03-1-HD040 and 313038-03-1-SB010 from the Korea Institute of Planning and Evaluation for Technology (iPET) of the Ministry of Food, Agriculture, Forestry and Fisheries, Republic of Korea. The ginseng sample used in this study was provided by the Ginseng Bank of Kyung Hee University.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© The Society for In Vitro Biology 2015

Authors and Affiliations

  • Sungeun Ahn
    • 1
  • Muhammad Hanif Siddiqi
    • 2
  • Veronica Castro Aceituno
    • 1
  • Shakina Yesmin Simu
    • 2
  • Jinglou Zhang
    • 2
  • Zuly Elizabeth Jimenez Perez
    • 2
  • Yu-Jin Kim
    • 1
  • Deok-Chun Yang
    • 1
    • 2
    • 3
  1. 1.Department of Oriental Medicinal Biotechnology, College of Life SciencesKyung Hee UniversityYonginRepublic of Korea
  2. 2.Ginseng Bank, Graduate School of Biotechnology, College of Life SciencesKyung Hee UniversityYonginRepublic of Korea
  3. 3.Department of Oriental Medicinal Materials and Processing, Graduate School of Biotechnology, College of Life ScienceKyung Hee UniversityYonginSouth Korea

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