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屋尘螨变应原 Der f 2 通过 p38 MAPK/NF-κB 信号通路驱动气道上皮细胞中 IL-6 和 GM-CSF 的表达。

House dust mite allergen Der f 2 drives IL-6 and GM-CSF expression in airway epithelial cells via p38 MAPK/NF-κB signaling.

机构信息

Division of Cardiovascular Surgery, Department of Surgery, China Medical University Hospital, Taichung, Taiwan.

Department of Medicine, School of Medicine, China Medical University, Taichung, Taiwan.

出版信息

J Asthma. 2024 Nov;61(11):1449-1458. doi: 10.1080/02770903.2024.2356685. Epub 2024 May 23.

Abstract

OBJECTIVE

Der f 2, a major allergen derived from , is a leading cause of allergic asthma. IL-6 and GM-CSF play essential roles in the exacerbation of asthma. However, the mechanical act by which Der f 2 mediates the expression of IL-6, IL-8, and GM-CSF in airway epithelial cells remains incompletely elucidated. Herein, we aimed to explore the effect of Der f 2 on IL-6 and GM-CSF expression in the human airway epithelial cell BEAS-2B and A549.

METHODS

Recombinant Der f 2 (rDf2) was acquired using . BEAS-2B and A549 cells were used as cell model. The expression of genes and proteins and the involvement of the signaling cascade were assessed using RT-PCR, quantitative real-time PCR (qPCR), Western blotting, and ELISA, respectively.

RESULTS

Our findings showed that rDf2 significantly induced mRNA expression and protein production of IL-6 and GM-CSF in BEAS-2B and A549 cells. In contrast, rDf2 did not influence IL-8 expression or production in both cells. Mechanistic studies revealed that rDf2 triggered activation of the p38 MAPK and JNK. Inhibition of p38, but not JNK, significantly attenuated rDf2-induced IL-6 and GM-CSF expression and production.

CONCLUSION

This study demonstrates that Der f 2 promotes the expression and production of the pro-inflammatory cytokines IL-6 and GM-CSF in airway epithelial cells via activation of the p38 signaling pathway. These findings provide insights into the molecular mechanisms that Der f 2 may exacerbate airway inflammation.

摘要

目的

Der f 2 是一种主要的过敏原,来源于 ,是导致过敏性哮喘的主要原因。IL-6 和 GM-CSF 在哮喘恶化中起着至关重要的作用。然而, Der f 2 介导气道上皮细胞中 IL-6、IL-8 和 GM-CSF 表达的机械作用仍未完全阐明。在此,我们旨在探讨 Der f 2 对人气道上皮细胞 BEAS-2B 和 A549 中 IL-6 和 GM-CSF 表达的影响。

方法

使用 获得重组 Der f 2(rDf2)。将 BEAS-2B 和 A549 细胞用作细胞模型。使用 RT-PCR、定量实时 PCR(qPCR)、Western 印迹和 ELISA 分别评估基因和蛋白的表达以及信号级联的参与情况。

结果

我们的研究结果表明,rDf2 显著诱导 BEAS-2B 和 A549 细胞中 IL-6 和 GM-CSF 的 mRNA 表达和蛋白产生。相比之下,rDf2 不影响两种细胞中 IL-8 的表达或产生。机制研究表明,rDf2 触发了 p38 MAPK 和 JNK 的激活。抑制 p38,但不抑制 JNK,可显著减弱 rDf2 诱导的 IL-6 和 GM-CSF 表达和产生。

结论

本研究表明, Der f 2 通过激活 p38 信号通路促进气道上皮细胞中促炎细胞因子 IL-6 和 GM-CSF 的表达和产生。这些发现为 Der f 2 可能加重气道炎症的分子机制提供了新的见解。

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