Chrysin Inhibits TNF alpha-Induced TSLP Expression through Downregulation of EGR1 Expression in Keratinocytes

Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that acts as a critical mediator in the pathogenesis of atopic dermatitis (AD). Various therapeutic agents that prevent TSLP function can efficiently relieve the clinical symptoms of AD. However, the downregulation of TSLP ex...

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Veröffentlicht in:International journal of molecular sciences 2021-04, Vol.22 (9), p.4350, Article 4350
Hauptverfasser: Yeo, Hyunjin, Lee, Young Han, Ahn, Sung Shin, Jung, Euitaek, Lim, Yoongho, Shin, Soon Young
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Sprache:eng
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Zusammenfassung:Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that acts as a critical mediator in the pathogenesis of atopic dermatitis (AD). Various therapeutic agents that prevent TSLP function can efficiently relieve the clinical symptoms of AD. However, the downregulation of TSLP expression by therapeutic agents remains poorly understood. In this study, we investigated the mode of action of chrysin in TSLP suppression in an AD-like inflammatory environment. We observed that the transcription factor early growth response (EGR1) contributed to the tumor necrosis factor alpha (TNF alpha)-induced transcription of TSLP. Chrysin attenuated TNF alpha-induced TSLP expression by downregulating EGR1 expression in HaCaT keratinocytes. We also showed that the oral administration of chrysin improved AD-like skin lesions in the ear and neck of BALB/c mice challenged with 2,4-dinitrochlorobenzene. We also showed that chrysin suppressed the expression of EGR1 and TSLP by inhibiting the extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2 mitogen-activated protein kinase pathways. Collectively, the findings of this study suggest that chrysin improves AD-like skin lesions, at least in part, through the downregulation of the ERK1/2 or JNK1/2-EGR1-TSLP signaling axis in keratinocytes.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22094350