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Artesunate attenuates 2, 4-dinitrochlorobenzene-induced atopic dermatitis by down-regulating Th17 cell responses in BALB/c mice.

Abstract
Steroidal agent is a standard clinical treatment of atopic dermatitis; however, have serious side effects. Artesunate is reported to exhibit anti-inflammatory properties although its effect on atopic eczema remains unknown. We investigated the therapeutic effects and possible mechanism of systemic artesunate on DNCB-induced atopic dermatitis in a BALB/c mouse model. To ascertain artesunate (5 and 10 mg/kg) efficacy, skin dermatitis severity and ear, spleen, and lymph node weight were evaluated. Skin tissue mRNA and protein expression and serum cytokine levels were examined. Artesunate significantly improved atopic dermatitis symptoms, decreasing the dermatitis score, ear weight difference, spleen weight, and lymph node weight compared with those following DNCB treatment. Artesunate reduced ear and skin epidermal thickness and mast cell infiltration, as determined using hematoxylin-eosin and toluidine blue staining, respectively. The basal level of IgE (287.67 ± 70.41 ng/ml) and TNF-α (19.94 ± 3.98 pg/ml) were Significantly elevated by DNCB (IgE: 1273.23 ± 176.53 ng/ml; TNF-α: 57.53 ± 3.87 pg/ml), while markedly been suppressed in the treatment group (AS-L: IgE: 1100.25 ± 135.32 ng/ml; TNF-α: 38.47 ± 3.26 pg/ml; AS-H: IgE: 459.46 ± 74.75 ng/ml; TNF-α: 24.38 ± 3.85 pg/ml). Among Th17 cell-related factors, DNCB treatment increased mRNA expression of IL-6, IL-17, IL-23, STAT3, and ROR-γt, but reduced TGF-β and SOCS 3; While artesunate reverse these changes. Compared with the model group, artesunate promoted SOCS3 protein and significantly inhibited ROR-γt protein and STAT3 phosphorylation. Thus, artesunate attenuates DNCB-induced atopic dermatitis by inhibiting the release of inflammatory cytokines and downregulating Th17 cell responses in atopic dermatitis mice.
AuthorsXin-Yu Bai, Ping Liu, Yee-Wen Chai, Yan Wang, Shuang-Hua Ren, Ying-Ying Li, Hong Zhou
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 874 Pg. 173020 (May 05 2020) ISSN: 1879-0712 [Electronic] Netherlands
PMID32087254 (Publication Type: Journal Article)
CopyrightCopyright © 2020 Elsevier B.V. All rights reserved.
Chemical References
  • Anti-Allergic Agents
  • Cytokines
  • Dinitrochlorobenzene
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Rorc protein, mouse
  • STAT3 Transcription Factor
  • Socs3 protein, mouse
  • Stat3 protein, mouse
  • Suppressor of Cytokine Signaling 3 Protein
  • Artesunate
Topics
  • Animals
  • Anti-Allergic Agents (pharmacology, therapeutic use)
  • Artesunate (pharmacology, therapeutic use)
  • Cell Line
  • Cytokines (blood, genetics, immunology)
  • Dermatitis, Atopic (drug therapy, immunology, pathology)
  • Dinitrochlorobenzene
  • Down-Regulation (drug effects)
  • Female
  • Humans
  • Mice, Inbred BALB C
  • Nuclear Receptor Subfamily 1, Group F, Member 3 (genetics, immunology)
  • STAT3 Transcription Factor (genetics, immunology)
  • Skin (drug effects, immunology, pathology)
  • Suppressor of Cytokine Signaling 3 Protein (genetics, immunology)
  • Th17 Cells (drug effects, immunology)

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