, Volume 41, Issue 2, pp 606–613 | Cite as

Oxymatrine Sensitizes the HaCaT Cells to the IFN-γ Pathway and Downregulates MDC, ICAM-1, and SOCS1 by Activating p38, JNK, and Akt

  • Chun-Jie Gao
  • Pei-Jun Ding
  • Li-Li Yang
  • Xu-Feng He
  • Meng-Jiao Chen
  • Dong-Ming Wang
  • Yan-Xin Tian
  • Hui-Min ZhangEmail author


Decreased interferon (IFN)-γ levels and increased levels of macrophage-derived chemokine (MDC) and intercellular adhesion molecule (ICAM)-1 are known to be involved in allergic skin diseases, such as eczema and atopic dermatitis. Activation of the IFN-γ and its downstream interleukin-12 (IL-12) pathway can correct these diseases. Suppressor of cytokine signaling 1 (SOCS1) is a cytokine signaling inhibitor that blocks downstream pathways of IFN-γ by blocking the mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) signaling pathways. Oxymatrine (OMT), a quinolizidine alkaloid extracted from the herbal medicine Radix Sophorae flavescentis, is used to treat allergic skin diseases in China. The non-cytotoxic concentrations of OMT in HaCaT cells were determined through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Tumor necrosis factor (TNF)-α and IFN-γ were used to stimulate HaCaT cells, and OMT was added to this system with tacrolimus (FK506) as a positive control. The mRNAs of cytokines, MDC, ICAM-1, IL-12p35, IL-12p40, and IFN-γ receptor (IFN-γR)α were detected by RT-PCR. Western blot analyses were performed to assess activation of the MAPK (p38, Jun N-terminal kinase, and extracellular signal-regulated kinase) and Akt signaling pathways. OMT increased the mRNA levels of the IL-12 and IFN-γRα, reduced the mRNA levels of ICAM-1, MDC, and SOCS1. But FK506 increased the mRNA levels of IL12 and inhibited the expression of ICAM-1 mRNAs and had no effects on the IFN-γRα, MDC, and SOCS1 mRNA in HaCaT cells stimulated with TNF-α and IFN-γ. Thus, the mechanisms through which OMT and FK506 ameliorate allergic skin diseases differ.


oxymatrine IFN-γ MAPKs SOCS1 allergic skin diseases atopic dermatitis 


Funding Information

This work was supported by the National Natural Science Foundation of China (NSFC; Grant No. 81302970/H2709) and the Shanghai Science and Technology Development Funds (Grant No. 13401902504).

Compliance with Ethical Standards

Competing Interests

The authors declare that they have no competing interests.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Chun-Jie Gao
    • 1
  • Pei-Jun Ding
    • 1
  • Li-Li Yang
    • 1
  • Xu-Feng He
    • 1
  • Meng-Jiao Chen
    • 1
  • Dong-Ming Wang
    • 1
  • Yan-Xin Tian
    • 1
  • Hui-Min Zhang
    • 1
    Email author
  1. 1.Department of DermatologyShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina

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