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


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.

SUBMITTER: Park Y 

PROVIDER: S-EPMC10458605 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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

Park Yukyung Y   Srigouri Huddar H   Kim Dongwon D  

Molecules (Basel, Switzerland) 20230818 16


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  ...[more]

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