House dust mite and Th2 cytokine-mediated epithelial barrier dysfunction attenuation by KL001 in 16-HBE cells.

IF 3.6 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Tissue Barriers Pub Date : 2024-01-02 Epub Date: 2023-04-20 DOI:10.1080/21688370.2023.2203841
Santhosh Kumar Duraisamy, Ashokkumar Srinivasan, Isaac Kirubakaran Sundar
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Abstract

House dust mite (HDM) is a common aeroallergen that can disrupt the airway epithelial barrier leading to dysregulated immune response, resulting in allergic lung diseases such as asthma. Cryptochrome (CRY), a circadian clock gene, plays an important role in the regulation of metabolism, and immune response. It remains unclear whether stabilizing CRY using KL001 can attenuate HDM/Th2 cytokine-induced epithelial barrier dysfunction in 16-HBE cells. We evaluate the effect of KL001 (20 µM) pre-treatment (4 hrs) in HDM/Th2 cytokine (IL-4 or IL-13)-mediated change in epithelial barrier function. HDM and Th2 cytokine-induced changes in transepithelial electrical resistance (TEER) were determined by an xCELLigence real-time cell analyzer and delocalization of adherens junction complex (AJC: E-cadherin and β-catenin) and tight junction proteins (TJP: Occludin and Zonula occludens-1) by immunostaining and confocal microscopy. Finally, quantitative real-time PCR (qRT-PCR) and Western blotting were used to measure altered gene expression and protein abundance of the epithelial barrier function and core clock genes, respectively. HDM and Th2 cytokine treatment significantly decreased TEER associated with altered gene expression and protein abundance of the selected epithelial barrier function and circadian clock genes. However, pre-treatment with KL001 attenuated HDM and Th2 cytokine-induced epithelial barrier dysfunction as early as 12-24 hrs. KL001 pre-treatment showed attenuation of HDM and Th2 cytokine-induced alteration in the localization and gene expression of AJP and TJP (Cdh1, Ocln, and Zo1) and core clock genes (Clock, Arntl/Bmal1, Cry1/2, Per1/2, Nr1d1/Rev-erbα, and Nfil3). We demonstrate, for the first time, the protective role of KL001 in HDM and Th2 cytokine-mediated epithelial barrier dysfunction.

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KL001 可减轻 16-HBE 细胞中屋尘螨和 Th2 细胞因子介导的上皮屏障功能障碍。
屋尘螨(HDM)是一种常见的空气过敏原,可破坏气道上皮屏障,导致免疫反应失调,引发哮喘等过敏性肺部疾病。隐色素(CRY)是一种昼夜节律时钟基因,在调节新陈代谢和免疫反应方面发挥着重要作用。目前还不清楚使用 KL001 稳定 CRY 是否能减轻 HDM/Th2 细胞因子诱导的 16-HBE 细胞上皮屏障功能障碍。我们评估了 KL001(20 µM)预处理(4 小时)对 HDM/Th2 细胞因子(IL-4 或 IL-13)介导的上皮屏障功能变化的影响。用 xCELLigence 实时细胞分析仪测定 HDM 和 Th2 细胞因子诱导的经上皮电阻(TEER)的变化,用免疫染色和共聚焦显微镜测定粘连接头复合体(AJC:E-cadherin 和 β-catenin)和紧密连接蛋白(TJP:Occludin 和 Zonula occludens-1)的脱定位。最后,利用实时定量 PCR(qRT-PCR)和 Western 印迹技术分别测量上皮屏障功能基因和核心时钟基因的基因表达和蛋白丰度变化。HDM和Th2细胞因子处理显著降低了与所选上皮屏障功能基因和昼夜节律时钟基因的基因表达和蛋白丰度改变相关的TEER。然而,KL001的预处理可减轻HDM和Th2细胞因子诱导的上皮屏障功能障碍,时间最早为12-24小时。KL001 预处理减轻了 HDM 和 Th2 细胞因子诱导的 AJP 和 TJP(Cdh1、Ocln 和 Zo1)以及核心时钟基因(Clock、Arntl/Bmal1、Cry1/2、Per1/2、Nr1d1/Rev-erbα 和 Nfil3)的定位和基因表达的改变。我们首次证明了 KL001 在 HDM 和 Th2 细胞因子介导的上皮屏障功能障碍中的保护作用。
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来源期刊
Tissue Barriers
Tissue Barriers MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.60
自引率
6.50%
发文量
25
期刊介绍: Tissue Barriers is the first international interdisciplinary journal that focuses on the architecture, biological roles and regulation of tissue barriers and intercellular junctions. We publish high quality peer-reviewed articles that cover a wide range of topics including structure and functions of the diverse and complex tissue barriers that occur across tissue and cell types, including the molecular composition and dynamics of polarized cell junctions and cell-cell interactions during normal homeostasis, injury and disease state. Tissue barrier formation in regenerative medicine and restoration of tissue and organ function is also of interest. Tissue Barriers publishes several categories of articles including: Original Research Papers, Short Communications, Technical Papers, Reviews, Perspectives and Commentaries, Hypothesis and Meeting Reports. Reviews and Perspectives/Commentaries will typically be invited. We also anticipate to publish special issues that are devoted to rapidly developing or controversial areas of research. Suggestions for topics are welcome. Tissue Barriers objectives: Promote interdisciplinary awareness and collaboration between researchers working with epithelial, epidermal and endothelial barriers and to build a broad and cohesive worldwide community of scientists interesting in this exciting field. Comprehend the enormous complexity of tissue barriers and map cross-talks and interactions between their different cellular and non-cellular components. Highlight the roles of tissue barrier dysfunctions in human diseases. Promote understanding and strategies for restoration of tissue barrier formation and function in regenerative medicine. Accelerate a search for pharmacological enhancers of tissue barriers as potential therapeutic agents. Understand and optimize drug delivery across epithelial and endothelial barriers.
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