Novel Quinazoline Derivative Induces Differentiation of Keratinocytes and Enhances Skin Barrier Functions against Th2 Cytokine-Mediated Signaling

新型喹唑啉衍生物诱导角质形成细胞分化并增强皮肤屏障功能以抵抗 Th2 细胞因子介导的信号传导

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作者:Yukyung Park, Huddar Srigouri, Dongwon Kim

Abstract

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by pruritic lesions and skin barrier dysfunction. In this study, we evaluated the effect of a quinazoline derivative, SH-340, on TSLP expression and signaling in human primary keratinocytes. Our results demonstrated that SH-340 significantly increased factors for differentiation and skin barrier function including KRT1, KRT2, KRT10, IVL, LOR, CLDN1, OVOL1, and FLG, whereas it inhibited TSLP expression in a dose-dependent manner, both at the mRNA and protein levels. Furthermore, SH-340 was found to inhibit the phosphorylation of STAT6, a downstream signaling molecule of IL-4 and IL-13, in keratinocytes. These findings suggest that SH-340 may suppress TSLP expression by inhibiting the IL-4/IL-13-STAT6 signaling pathway. Finally, SH-340 may potentially contribute to both the alleviation of inflammation and the restoration of skin barrier function.

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