KRT6A inhibits IL-1β-mediated pyroptosis of keratinocytes via blocking IL-17 signaling

IF 1.5 4区医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Critical Reviews in Eukaryotic Gene Expression Pub Date : 2023-12-01 DOI:10.1615/critreveukaryotgeneexpr.2023050039

Yuan Li, Qi Wu

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引用次数: 0

Abstract

Keratin 6A (KRT6A) is involved in the pathogenesis of various skin diseases. However, the reports on the roles of KRT6A in atopic dermatitis (AD) are limited. This study aimed to investigate the potentials of KRT6A in AD. mRNA levels were detected by RT-PCR. Cytokine release was determined by ELISA. Protein expression was determined using western blot. Cell viability was determined by CCK-8. Cytotoxicity was detected by LDH assay. Cell death was determined by TUNEL. The pyroptosis of keratinocytes was detected using flow cytometry. We found that KRT6A was overexpressed in AD patients. Moreover, KRT6A was stimulated after exposed to proinflammatory cytokines. Overexpressed KRT6A suppressed inflammatory response, while KRT6A knockdown exerted the opposite effects. Overexpressed KRT6A suppressed inflammation-induced pyroptosis of keratinocytes. Additionally, KRT6A negatively regulated IL-17A expression, blocking IL-17 signaling. IL-17a overexpression antagonized the effects of KRT6A and promoted pyroptosis of keratinocytes. In conclusion, KRT6A exerted protective functions in AD via regulating IL-17 signaling. This KRT6A/IL-17 may be a novel target for AD.

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KRT6A通过阻断IL-17信号传导抑制il -1β介导的角化细胞焦亡

角蛋白6A (KRT6A)参与多种皮肤病的发病机制。然而，关于KRT6A在特应性皮炎(AD)中的作用的报道有限。本研究旨在探讨KRT6A在AD中的潜在作用。RT-PCR检测mRNA水平。ELISA法检测细胞因子释放量。western blot检测蛋白表达。CCK-8检测细胞活力。LDH法检测细胞毒性。TUNEL法测定细胞死亡情况。流式细胞术检测角质形成细胞的焦亡。我们发现KRT6A在AD患者中过表达。此外，KRT6A在暴露于促炎细胞因子后受到刺激。KRT6A过表达抑制炎症反应，而KRT6A敲低则发挥相反的作用。过表达KRT6A抑制炎症诱导的角化细胞焦亡。此外，KRT6A负调控IL-17A表达，阻断IL-17信号传导。IL-17a过表达可拮抗KRT6A的作用，促进角质形成细胞的焦亡。综上所述，KRT6A通过调节IL-17信号通路在AD中发挥保护作用。这个KRT6A/IL-17可能是AD的新靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物

CiteScore

2.70

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.