Role of diesel exhaust particle-induced cellular senescence in the development of asthma in young and old mice

IF 6.2 2区 医学 Q1 ALLERGY Allergology International Pub Date : 2024-02-12 DOI:10.1016/j.alit.2024.01.010
Hyun Seung Lee , Heung-Woo Park
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Abstract

Background

Although it has been reported that cellular senescence is important in the pathogenesis of asthma, the differential effects of diesel exhaust particle (DEP)-induced cellular senescence on the development of asthma according to age have not been thoroughly studied.

Methods

We first confirmed that DEP induced cellular senescence in mouse lungs, and then that DEP-induced cellular senescence followed by intranasal instillation of a low-dose house dust mite (HDM) allergen resulted in murine asthma. Second, we examined age-dependent differential effects using 6-week-old (young) and 18-month-old mice (old), and tested whether the mammalian target of the rapamycin (mTOR) pathway plays an important role in this process. Finally, we performed in vitro experiments using human bronchial epithelial cells (HBEC) originating from young and elderly adults to identify the underlying mechanisms.

Results

DEP induced cellular senescence in the airway epithelial cells of young and old mice characterized by increased senescence-associated beta-galactosidase, S100A8/9, and high mobility group box 1 (HMGB1) expressions. DEP-induced cellular senescence with subsequent exposure to a low-dose HDM allergen resulted in asthma in young and old mice. Rapamycin (mTOR pathway inhibitor) administration before DEP instillation significantly attenuated these asthmatic features. In addition, after treatment with a low-dose HDM allergen, S100A9 and HMGB1 over-expressed HBEC originating from young and elderly adults greatly activated co-cultured monocyte-derived dendritic cells (DCs).

Conclusions

This study showed that DEP-induced senescence made both young and old mice susceptible to allergic sensitization and resultant asthma development by enhancing DC activation. Public health efforts to reduce DEP exposure are warranted.

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柴油废气颗粒诱导的细胞衰老在年轻和年老小鼠哮喘发病中的作用。
背景:尽管有报道称细胞衰老在哮喘的发病机制中起着重要作用,但柴油机废气颗粒(DEP)诱导的细胞衰老对不同年龄哮喘发病的不同影响尚未得到深入研究:方法:我们首先证实了柴油机废气微粒(DEP)诱导小鼠肺部细胞衰老,然后证实了在柴油机废气微粒诱导细胞衰老后鼻内灌注低剂量屋尘螨(HDM)过敏原会导致小鼠哮喘。其次,我们使用 6 周大的小鼠(幼鼠)和 18 个月大的小鼠(老 鼠)研究了年龄依赖性差异效应,并测试了雷帕霉素哺乳动物靶标(mTOR)通路是否在这一过程中发挥了重要作用。最后,我们使用来自年轻人和老年人的人类支气管上皮细胞(HBEC)进行了体外实验,以确定其潜在机制:结果:DEP诱导了年轻和老年小鼠气道上皮细胞的细胞衰老,衰老相关的β-半乳糖苷酶、S100A8/9和高迁移率组框1(HMGB1)表达增加。DEP诱导的细胞衰老与随后暴露于低剂量HDM过敏原会导致年轻和年老小鼠发生哮喘。在灌入 DEP 之前服用雷帕霉素(mTOR 途径抑制剂)可显著减轻这些哮喘特征。此外,经低剂量 HDM 过敏原处理后,S100A9 和 HMGB1 过度表达的来自年轻人和老年人的 HBEC 能极大地激活共培养的单核细胞衍生树突状细胞(DCs):本研究表明,DEP诱导的衰老通过增强DC的活化作用,使年轻和年老的小鼠都容易对过敏过敏,并导致哮喘的发生。因此有必要在公共卫生方面做出努力,减少与 DEP 的接触。
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来源期刊
Allergology International
Allergology International ALLERGY-IMMUNOLOGY
CiteScore
12.60
自引率
5.90%
发文量
96
审稿时长
29 weeks
期刊介绍: Allergology International is the official journal of the Japanese Society of Allergology and publishes original papers dealing with the etiology, diagnosis and treatment of allergic and related diseases. Papers may include the study of methods of controlling allergic reactions, human and animal models of hypersensitivity and other aspects of basic and applied clinical allergy in its broadest sense. The Journal aims to encourage the international exchange of results and encourages authors from all countries to submit papers in the following three categories: Original Articles, Review Articles, and Letters to the Editor.
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