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.
Matched MeSH terms: Nuclear Receptor Subfamily 1, Group F, Member 3/immunology
The Runx1 transcription factor cooperates with or antagonizes other transcription factors and plays essential roles in the differentiation and function of T lymphocytes. Previous works showed that Runx1 is expressed in peripheral CD4(+) T cells which level declines after T cell receptor (TCR) activation, and artificial deletion of Runx1 causes autoimmune lung disease in mice. The present study addresses the mechanisms by which Runx1 contributes to the maintenance of peripheral CD4(+) T cell quiescence. Microarray and quantitative RT-PCR analyses were employed to compare the transcriptome of Runx1 -/- CD4(+) T cells to those of unstimulated and TCR-stimulated Runx1 +/- cells. The results identified genes whose expression was modulated similarly by Runx1 deletion and TCR activation. Among them, genes encoding cytokines, chemokines, and Jak/STAT signaling molecules were substantially induced. In Runx1-deleted T cells, simultaneous increases in Il-17A and Rorγc, a known master gene in TH17 differentiation, were observed. In addition, we observed that the loss of Runx1 reduced the transcription of genes encoding quiescence-associated transcription factors, including Foxp1, Foxo1, and Klf2. Interestingly, we identified consensus Runx1 binding sites at the promoter regions of Foxp1, Foxo1, and Klf2 genes, which can be enriched by chromatin immunoprecipitation assay with an anti-Runx1 antibody. Therefore, we suggest that Runx1 may activate, directly or indirectly, the expression of quiescence-associated molecules and thereby contribute to the maintenance of quiescence in CD4(+) T cells.
Matched MeSH terms: Nuclear Receptor Subfamily 1, Group F, Member 3/immunology