Open Access

Shikonin inhibits CEBPD downregulation in IL‑17‑treated HaCaT cells and in an imiquimod‑induced psoriasis model

  • Authors:
    • Xiao‑Ou Lan
    • He‑Xiao Wang
    • Rui‑Qun Qi
    • Yuan‑Yuan Xu
    • Ya‑Jie  Yu
    • Yang Yang
    • Hao Guo
    • Xing‑Hua Gao
    • Long Geng
  • View Affiliations

  • Published online on: July 9, 2020     https://doi.org/10.3892/mmr.2020.11315
  • Pages: 2263-2272
  • Copyright: © Lan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Psoriasis is a chronic inflammatory skin disease characterized by well‑defined scaly papules and plaques. Interleukin (IL)‑17 is involved in its pathogenesis and promotes the proliferation of epidermal keratinocytes through signal transducer and activator of transcription 3 (STAT3) activation. Shikonin, a natural naphthoquinone isolated from Lithospermum erythrorhizon, possesses anti‑inflammatory and immunosuppressive properties and can suppress IL‑17‑induced vascular endothelial growth factor expression by inhibiting the JAK/STAT3 pathway. In the present study, MTS, iCELLigence and RT‑qPCR were used to determine the optimal concentration and duration of IL‑17 or shikonin acting on HaCaT cells. The changes in the expression levels of genes associated with the IL‑6/STAT3 pathway in differentially treated cells were analyzed via RT2Profiler™ PCR Array. Small interfering RNA was used to silence the expression levels of the target gene CCAAT/enhancer‑binding protein δ (CEBPD). Western blotting and immunohistochemistry were used to evaluate the effect of shikonin on imiquimod‑induced psoriasis in mice and the expression levels of CEBPD. Shikonin reversed IL‑17‑mediated downregulation of the tumor suppressor CEBPD in HaCaT cells. Moreover, low levels of CEBPD in the imiquimod‑induced mouse model of psoriasis were restored by shikonin treatment, which ameliorated excessive keratinocyte proliferation. Taken together, these findings suggest that CEBPD plays a key role in the pathogenesis of psoriasis and can be targeted by shikonin as a potential therapeutic strategy.
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September-2020
Volume 22 Issue 3

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Lan XO, Wang HX, Qi RQ, Xu YY, Yu YJ, Yang Y, Guo H, Gao XH and Geng L: Shikonin inhibits CEBPD downregulation in IL‑17‑treated HaCaT cells and in an imiquimod‑induced psoriasis model. Mol Med Rep 22: 2263-2272, 2020.
APA
Lan, X., Wang, H., Qi, R., Xu, Y., Yu, Y., Yang, Y. ... Geng, L. (2020). Shikonin inhibits CEBPD downregulation in IL‑17‑treated HaCaT cells and in an imiquimod‑induced psoriasis model. Molecular Medicine Reports, 22, 2263-2272. https://doi.org/10.3892/mmr.2020.11315
MLA
Lan, X., Wang, H., Qi, R., Xu, Y., Yu, Y., Yang, Y., Guo, H., Gao, X., Geng, L."Shikonin inhibits CEBPD downregulation in IL‑17‑treated HaCaT cells and in an imiquimod‑induced psoriasis model". Molecular Medicine Reports 22.3 (2020): 2263-2272.
Chicago
Lan, X., Wang, H., Qi, R., Xu, Y., Yu, Y., Yang, Y., Guo, H., Gao, X., Geng, L."Shikonin inhibits CEBPD downregulation in IL‑17‑treated HaCaT cells and in an imiquimod‑induced psoriasis model". Molecular Medicine Reports 22, no. 3 (2020): 2263-2272. https://doi.org/10.3892/mmr.2020.11315