大气细颗粒物通过TLR4/NF-κB通路诱导鼻黏膜上皮细胞炎症反应

doi:10.6040/j.issn.1671-7554.0.2023.0524

山东大学学报 (医学版) ›› 2023, Vol. 61 ›› Issue (9): 47-55.doi: 10.6040/j.issn.1671-7554.0.2023.0524

大气细颗粒物通过TLR4/NF-κB通路诱导鼻黏膜上皮细胞炎症反应

杨晓喆^1,2,赵妍^1,2,青卉³,王向东^1,2,3,张罗^1,2,3

1.首都医科大学附属北京同仁医院耳鼻咽喉头颈外科, 耳鼻咽喉头颈科学教育部重点实验室(首都医科大学), 北京 100730;2. 北京市耳鼻咽喉科研究所, 过敏性疾病北京实验室, 鼻病研究北京市重点实验室, 北京 100005;3. 首都医科大学附属北京同仁医院变态反应科, 北京 100730

收稿日期:2023-06-17 发布日期:2023-10-10
通讯作者: 张罗. E-mail:dr.luozhang@139.com 王向东. E-mail:entwxd@vip.sina.com
基金资助:
国家重点研发计划(2022YFC2504100);教育部长江学者与创新团队发展计划(IRT13082),中国医学科学院医学与健康科技创新工程项目(2019-I2M-5-022);首都临床特色诊疗技术研究及转化应用重点项目(Z211100002921057);首都卫生发展科研专项重点攻关项目(2022-1-1091);国家自然科学基金(82101190,82171110,82000962,81970852);北京市自然科学基金(7222024);北京市卫生系统高层次公共卫生人才建设项目领军人才(领军人才-01-08,领军人才-02-09);北京市医管中心“青苗”人才计划(QML20230201)

PM_2.5 induces inflammatory response in nasal epithelial cells through TLR4/NF-κB pathway

YANG Xiaozhe^1,2, ZHAO Yan^1,2, QING Hui³, WANG Xiangdong^1,2,3, ZHANG Luo^1,2,3

1. Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology Head and Neck Surgery(Capital Medical University), Ministry of Education, Beijing 100730, China;
2. Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Municipal Education Commission, Beijing Key Laboratory of Nasal Diseases, Beijing 100005, China;
3. Department of Allergy, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China

Received:2023-06-17 Published:2023-10-10

摘要/Abstract

摘要： 目的探讨阐明TLR4/NF-κB信号通路在PM_2.5诱导鼻黏膜上皮细胞炎症反应中的作用机制。方法参考健康人鼻黏膜上皮细胞系(HNEpCs)构建PM_2.5暴露模型。暴露后提取RNA利用Illumina测序仪进行转录组分析。荧光定量PCR(qRT-PCR)分析TLR4、NFKB1、NFKB1A基因的RNA表达水平。结果 PM_2.5可引起HNEpCs毒性及转录组异常调控,导致TLR4、NFKBIA及IL1B基因的异常表达,KEGG通路分析发现所参与的TLR4/NF-κB通路显著富集。qRT-PCR验证实验发现,经过PM_2.5暴露后TLR4基因上调,NFKB1基因下调,与此同时抑制NF-κB的NFKB1A(NF-κB抑制因子α)显著下调,故而在一定程度上导致TLR4/NF-κB通路异常调控。结论本研究发现HNEpCs在PM_2.5暴露后,TLR4/NF-κB通路异常调控,可能在PM_2.5暴露所诱发的鼻黏膜炎症反应中起到关键作用。

关键词: 鼻黏膜上皮细胞系, 大气细颗粒物, 暴露模型, 基因异常表达, 荧光定量分析, 转录组分析, 鼻黏膜炎症

Abstract: Objective To investigate the mechanism of TLR4/NF-κB signaling pathway in the inflammatory response of nasal mucosal epithelial cells induced by fine particulate matter(PM_2.5). Methods After healthy human nasal epithelial cells(HNEpCs)were exposed to PM_2.5, the RNA was extracted for transcriptome analysis by Illumina sequencer. The expressions of TLR4, NFKB1 and NFKB1A were detected with quantitative real-time PCR(qRT-PCR). Results PM_2.5 caused cell toxicity and abnormal regulation of transcriptome of HNEpCs, and abnormal expressions of TLR4, NFKBIA and IL1B. KEGG pathway analysis indicated that TLR4/NF-κB pathway was significantly enriched. The qRT-PCR validation experiment revealed that after PM_2.5 exposure, TLR4 was up-regulated while NFKB1 was down-regulated, and NFKBIA,which inhibited NF-κB, was significantly down-regulated, thus leading to abnormal regulation of the TLR4/NF-κB pathway. Conclusion The abnormal regulation of TLR4/NF-κB in HNEpCs may play a crucial role in the nasal mucosa inflammatory response induced by PM_2.5 exposure.

Key words: Nasal epithelial cell line, Fine particulate matter, Exposure model, Abnormal regulation of gene, Quantitative red-time, Transcriptome analysis, Nasal mucosa inflammation

中图分类号:

R765.25

杨晓喆,赵妍,青卉,王向东,张罗. 大气细颗粒物通过TLR4/NF-κB通路诱导鼻黏膜上皮细胞炎症反应[J]. 山东大学学报 (医学版), 2023, 61(9): 47-55.

YANG Xiaozhe, ZHAO Yan, QING Hui, WANG Xiangdong, ZHANG Luo. PM_2.5 induces inflammatory response in nasal epithelial cells through TLR4/NF-κB pathway[J]. Journal of Shandong University (Health Sciences), 2023, 61(9): 47-55.

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大气细颗粒物通过TLR4/NF-κB通路诱导鼻黏膜上皮细胞炎症反应

PM_2.5 induces inflammatory response in nasal epithelial cells through TLR4/NF-κB pathway

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大气细颗粒物通过TLR4/NF-κB通路诱导鼻黏膜上皮细胞炎症反应

PM2.5 induces inflammatory response in nasal epithelial cells through TLR4/NF-κB pathway

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PM_2.5 induces inflammatory response in nasal epithelial cells through TLR4/NF-κB pathway