Frontiers in Pharmacology (Aug 2021)

Dihydroartemisinin Alleviates Imiquimod-Induced Psoriasis-like Skin Lesion in Mice Involving Modulation of IL-23/Th17 Axis

  • Jiang-Min Liu,
  • Quan-Xin Jin,
  • Manabu Fujimoto,
  • Fang-Fang Li,
  • Lin-Bo Jin,
  • Ran Yu,
  • Guang-Hai Yan,
  • Lian-Hua Zhu,
  • Fan-Ping Meng,
  • Qing-Gao Zhang,
  • Gui-Hua Jin

DOI
https://doi.org/10.3389/fphar.2021.704481
Journal volume & issue
Vol. 12

Abstract

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Background: Psoriasis is a T help 17 (Th17) cell-mediated chronic inflammatory skin disease. Recent studies have shown that dihydroartemisinin (DHA) can significantly reduce experimental autoimmune encephalomyelitis and rheumatoid arthritis by regulating Th17 cells.Objective: To verify whether DHA can improve the symptoms of psoriasis and to further explore the possible mechanism.Methods: The efficiency of DHA was preliminary detected on human keratinocytes (HaCaT) cells in psoriatic condition. Then, imiquimod-induced psoriasis-like model in BALB/c mice was established to evaluate the effects of DHA in vivo.Results: Under the stimulation of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), DHA inhibited the proliferation of HaCaT cells and significantly affected the mRNA expression levels of IFN-γ, interleukin (IL), IL-17A and IL-23. DHA treatment reduced the severity of psoriasis-like skin and resulted in less infiltration of immune cells in skin lesions. DHA restored the expression of IFN-γ, IL-17A, and IL-23 in skins, as well as a decrease of cytokines and chemokines in skin supernatant. DHA also altered the cellular composition in the spleen, which is the makeup of the T cells, dendritic cells (DCs), and macrophages. DHA recovered Th17-related profile with decreased frequency of IL-17+CD4+T cells from splenocyte of mice. Furthermore, DHA also inhibited the concentration of IL-17 from Th17 cells and the expression of Th17 cell-related transcription factors retinoid-related orphan receptor-gamma t (ROR-γt) in vitro. In addition, phosphorylation of signal transducer and activator of transcription-3 (STAT3) was significantly reduced in DHA treatment mice, suggesting that the IL-23/Th17 axis plays a pivotal role.Conclusion: DHA inhibits the progression of psoriasis by regulating IL-23/Th17 axis and is expected to be an effective drug for the treatment of psoriasis.

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