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诱导痰中 CXCL14 水平升高与哮喘患者的嗜酸性粒细胞炎症和气道阻塞有关。

Elevated CXCL14 in Induced Sputum Was Associated with Eosinophilic Inflammation and Airway Obstruction in Patients with Asthma.

机构信息

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Institute of Respiratory Diseases of Sun Yat-Sen University, Guangzhou, China.

出版信息

Int Arch Allergy Immunol. 2022;183(11):1216-1225. doi: 10.1159/000526367. Epub 2022 Sep 5.

DOI:10.1159/000526367
PMID:36063806
Abstract

INTRODUCTION

CXCL14 involved in inflammatory processes was upregulated in the asthma expression profile datasets in our pilot study. However, the expression of CXCL14 in induced sputum and its potential clinical role in asthma were poorly reported.

OBJECTIVE

We sought to detect CXCL14 expression in airway epithelium and induced sputum cells of asthma and explore its potential clinical implications.

METHODS

The expression of CXCL14 in asthma was analyzed using R software based on multiple microarray datasets, including GSE43696, GSE63142, GSE67940, and GSE76262. Subsequent verification of the CXCL14 expression pattern in induced sputum and bronchial epithelium cells was performed by qRT-PCR and ELISA. Besides, the correlations between CXCL14 and eosinophilic inflammation indicators (FeNO, EOS#, and IgE), Th2 signature genes (SERPINB2, POSTN, and CLCA1), inflammatory cytokines (IL-4, IL-5, IL-10, IL-13, IL-25, IL-33, TSLP, IL-8, IL-17A, IFN-γ, and IL-2), and airway obstruction indicators (pulmonary function and mucin secretion) were further explored.

RESULTS

The expression of CXCL14 in epithelium and sputum cells was upregulated in asthma and positively correlated with clinical eosinophilic indicators. The protein levels of CXCL14 were positively associated with Th2 signature genes (SERPINB2, POSTN, and CLCA1) and Th2 cytokines (IL-4, IL-5, IL-10, IL-13, IL-25, IL-33, and TSLP). Increased expression of CXCL14 was also observed in BEAS-2B cells stimulated by the cytokine IL-4. Furthermore, the expression of CXCL14 was positively correlated with MUC5AC secretion and negatively associated with pulmonary function.

CONCLUSIONS

Upregulated CXCL14 in asthma was positively correlated with inflammatory indicators and negatively correlated with pulmonary function, which indicated that upregulated CXCL14 might act as a pathogenic gene through involvement in Th2 inflammation in asthma.

摘要

简介

在我们的初步研究中,CXCL14 参与炎症过程,在哮喘表达谱数据集中上调。然而,CXCL14 在诱导痰中的表达及其在哮喘中的潜在临床作用报道甚少。

目的

我们试图检测哮喘患者气道上皮细胞和诱导痰细胞中 CXCL14 的表达,并探讨其潜在的临床意义。

方法

基于多个微阵列数据集,包括 GSE43696、GSE63142、GSE67940 和 GSE76262,使用 R 软件分析哮喘患者 CXCL14 的表达。随后通过 qRT-PCR 和 ELISA 验证诱导痰和支气管上皮细胞中 CXCL14 的表达模式。此外,还进一步探讨了 CXCL14 与嗜酸性粒细胞炎症指标(FeNO、EOS#和 IgE)、Th2 特征基因(SERPINB2、POSTN 和 CLCA1)、炎症细胞因子(IL-4、IL-5、IL-10、IL-13、IL-25、IL-33、TSLP、IL-8、IL-17A、IFN-γ和 IL-2)和气道阻塞指标(肺功能和粘蛋白分泌)之间的相关性。

结果

CXCL14 在哮喘患者的上皮细胞和痰细胞中的表达上调,且与临床嗜酸性粒细胞指标呈正相关。CXCL14 的蛋白水平与 Th2 特征基因(SERPINB2、POSTN 和 CLCA1)和 Th2 细胞因子(IL-4、IL-5、IL-10、IL-13、IL-25、IL-33 和 TSLP)呈正相关。在细胞因子 IL-4 刺激的 BEAS-2B 细胞中也观察到 CXCL14 的表达增加。此外,CXCL14 的表达与 MUC5AC 分泌呈正相关,与肺功能呈负相关。

结论

哮喘患者中上调的 CXCL14 与炎症指标呈正相关,与肺功能呈负相关,表明上调的 CXCL14 可能通过参与哮喘中的 Th2 炎症而作为一个致病基因。

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