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人类上皮细胞中屋尘螨过敏原的多重转录谱分析

Multiplexed transcriptional profiling of Dermatophagoides house dust mites allergens in human epithelium cells.

作者信息

Lin Chia-Yang, Cheng Chun-Wen, Ko Jiunn-Liang, Lue Ko-Huang, Liu Yu-Fan

机构信息

Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Department of Family Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.

出版信息

Environ Toxicol. 2024 Apr;39(4):2229-2239. doi: 10.1002/tox.24109. Epub 2023 Dec 21.

Abstract

Allergic asthma, a chronic disease characterized by airway inflammation, poses a significant public health concern. It is well-established that house dust mites (HDMs) are common inducers of allergic responses in individuals, particularly children. In central Taiwan, our research team observed that over 80% of allergic children exhibited sensitization to various HDMs species. This investigation aims to bridge the gap between these observations and a better understanding of the early fundamental mechanisms for preventing allergic diseases. Specifically, our study delves into the impact of crude extracts of HDMs on human epithelial BEAS-2B cells. Our findings, based on RNA sequencing (RNA-seq) analysis, shed light on how three major Dermatophagoides HDMs allergens activate a common Toll-like receptor signaling pathway in human epithelial cells within a 4-h treatment. During this process, the nuclear transcription factor NF-κB translocated into the cell nucleus within 30 min of allergen stimulation, triggering the expression of pro-inflammatory genes such as IL-6 and IL-8 over 4 h. Additionally, when the cells were treated with specific Dermatophagoides microceras (Der m) allergens, it resulted in the upregulation of genes that regulate type 1 diabetes mellitus (T1DM) signaling pathways. This led to the mediation of IL-12A inflammation. Furthermore, there was an increase in gene sets associated with cilia function and the microtubule cytoskeleton in human epithelial cells after treatment with a combination of Der m allergens and Dexamethasone. Additionally, OMICs analysis was conducted to examine the effects of HDMs allergenic stimulation on human epidermal cells. We aimed to improve our understanding of the molecular mechanisms within cells and identify potential targets and natural products in the treatment of asthma caused by HDMs allergens.

摘要

过敏性哮喘是一种以气道炎症为特征的慢性疾病,引起了重大的公共卫生关注。众所周知,屋尘螨(HDMs)是个体尤其是儿童过敏反应的常见诱导因素。在台湾中部,我们的研究团队观察到超过80%的过敏儿童对多种HDMs物种过敏。这项研究旨在弥合这些观察结果与更好地理解预防过敏性疾病的早期基本机制之间的差距。具体而言,我们的研究深入探讨了HDMs粗提物对人上皮BEAS-2B细胞的影响。我们基于RNA测序(RNA-seq)分析的结果揭示了三种主要的尘螨属HDMs过敏原如何在4小时的处理过程中激活人上皮细胞中常见的Toll样受体信号通路。在此过程中,核转录因子NF-κB在过敏原刺激后30分钟内转移到细胞核内,在4小时内触发促炎基因如IL-6和IL-8的表达。此外,当细胞用特异性的微小屋尘螨(Der m)过敏原处理时,导致调节1型糖尿病(T1DM)信号通路的基因上调。这导致了IL-12A炎症的介导。此外,在用Der m过敏原和地塞米松联合处理后人上皮细胞中与纤毛功能和微管细胞骨架相关的基因集增加。此外,进行了组学分析以检查HDMs过敏原刺激对人表皮细胞的影响。我们旨在增进对细胞内分子机制的理解,并确定治疗由HDMs过敏原引起的哮喘的潜在靶点和天然产物。

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