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约氏乳杆菌N5上清液保护RPMI-2650细胞免受HDM诱导的损伤,其作用与抑制NR4A1-IRE1-XBP1介导的未折叠蛋白反应相关。

Lactobacillus johnsonii N5 Supernatant Protects RPMI-2650 Cells from HDM-Induced Injury in Association with Suppression of the NR4A1-IRE1-XBP1-Mediated Unfolded Protein Response.

基础研究鼻科IF 4.5Q2

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中文摘要

背景/目的: 屋尘螨(HDM)是重要的过敏原,可导致鼻上皮细胞损伤,并在过敏性鼻炎的病理生理学中发挥作用。约氏乳杆菌N5上清液(N5sup)是一种益生菌菌株,可能具有保护特性;然而,其涉及的分子过程仍不清楚。方法:将RPMI-2650人鼻上皮癌细胞分别接受HDM、N5sup或两者联合处理。结果:HDM刺激诱导了一定程度的转录改变。与对照组相比,HDM处理的细胞中共鉴定出221个差异表达基因,这些基因主要富集于未折叠蛋白反应(UPR)通路的IRE1-XBP1分支。综合研究表明,HDM增加了NR4A1-IRE1-XBP1信号通路,表现为NR4A1、ERN1(IRE1)和XBP1表达水平升高。qRT-PCR和Western blotting均证实,N5sup强烈抑制了HDM诱导的NR4A1、IRE1和XBP1升高。蛋白质-蛋白质相互作用网络分析进一步证实了一个由NR4A1、IRE1和XBP1组成的中心枢纽。结论:N5sup上清液保护RPMI-2650细胞免受HDM诱导的损伤,这种保护作用与NR4A1-IRE1-XBP1通路相关。这些发现表明,该信号轴可能作为益生菌干预过敏性气道疾病的潜在治疗靶点。

英文摘要

Background/Objectives: House dust mites (HDMs) are significant allergens that cause damage to nasal epithelial cells and have a role in the pathophysiology of allergic rhinitis. Lactobacillus johnsonii N5 supernatant (N5sup), a probiotic strain, exhibits possible protective properties; nevertheless, the molecular processes involved remain unclear. Methods: RPMI-2650 human nasal epithelial carcinoma cells were subjected to treatment with HDM, N5sup, or a combination of both. Results: The HDM stimulation induced a certain degree of transcriptional alterations. Compared with the control group, a total of 221 differentially expressed genes were identified in HDM-treated cells, which were mainly enriched in the IRE1-XBP1 branch of the unfolded protein response (UPR) pathway. Comprehensive investigation demonstrated that HDM increased the NR4A1-IRE1-XBP1 signaling pathway, characterized by elevated expression levels of NR4A1, ERN1 (IRE1), and XBP1. Both qRT-PCR and Western blotting verified that N5sup strongly inhibited the HDM-induced increase in NR4A1, IRE1, and XBP1. Analysis of the protein-protein interaction network further confirmed a central hub comprising NR4A1, IRE1, and XBP1. Conclusions: N5sup supernatant protects RPMI-2650 cells from HDM-induced injury, and this protective effect is associated with the NR4A1-IRE1-XBP1 pathway. These findings suggest that this signaling axis may serve as a potential therapeutic target for probiotic intervention in allergic airway diseases.