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柴油废气颗粒暴露对大豆所致小鼠哮喘模型的影响。

Effects of diesel exhaust particle exposure on a murine model of asthma due to soybean.

作者信息

Alvarez-Simón Daniel, Muñoz Xavier, Gómez-Ollés Susana, de Homdedeu Miquel, Untoria María-Dolores, Cruz María-Jesús

机构信息

Pulmonology Service, Hospital Universitari Vall d'Hebron, Barcelona, Spain.

Medicine Department Universitat Autònoma de Barcelona, Barcelona, Spain.

出版信息

PLoS One. 2017 Jun 19;12(6):e0179569. doi: 10.1371/journal.pone.0179569. eCollection 2017.

Abstract

BACKGROUND

Exposure to soybean allergens has been linked to asthma outbreaks. Exposure to diesel exhaust particles (DEP) has been associated with an increase in the risk of asthma and asthma exacerbation; however, in both cases the underlying mechanisms remain poorly understood, as does the possible interaction between the two entities.

OBJECTIVE

To investigate how the combination of soybean allergens and DEP can affect the induction or exacerbation of asthma in a murine model.

METHODS

BALB/c mice received intranasal instillations of saline, 3 or 5 mg protein/ml soybean hull extract (SHE), or a combination of one of these three solutions with DEP. Airway hyperresponsiveness (AHR), pulmonary inflammation in bronchoalveolar lavage, total serum immunoglobulin E and histological studies were assessed.

RESULTS

A 5 mg protein/ml SHE solution was able by itself to enhance AHR (p = 0.0033), increase eosinophilic inflammation (p = 0.0003), increase levels of IL-4, IL-5, IL-13, IL-17A, IL-17F and CCL20, and reduce levels of IFN-γ. The combination of 5 mg protein/ml SHE with DEP also produced an increase in AHR and eosinophilic inflammation, but presented a slightly different cytokine profile with higher levels of Th17-related cytokines. However, while the 3 mg protein/ml SHE solution did not induce asthma, co-exposure with DEP resulted in a markedly enhanced AHR (p = 0.002) and eosinophilic inflammation (p = 0.004), with increased levels of IL-5, IL-17F and CCL20 and decreased levels of IFN-γ.

CONCLUSIONS & CLINICAL RELEVANCE: The combination of soybean allergens and DEP is capable of triggering an asthmatic response through a Th17-related mechanism when the soybean allergen concentration is too low to promote a response by itself. DEP monitoring may be a useful addition to allergen monitoring in order to prevent new asthma outbreaks.

摘要

背景

接触大豆过敏原与哮喘发作有关。接触柴油废气颗粒(DEP)与哮喘风险增加及哮喘恶化相关;然而,在这两种情况下,其潜在机制仍知之甚少,二者之间可能存在的相互作用亦是如此。

目的

研究大豆过敏原与DEP的组合如何在小鼠模型中影响哮喘的诱发或加重。

方法

BALB/c小鼠经鼻内滴注生理盐水、3或5毫克蛋白质/毫升大豆皮提取物(SHE),或这三种溶液之一与DEP的组合。评估气道高反应性(AHR)、支气管肺泡灌洗中的肺部炎症、血清总免疫球蛋白E及组织学研究。

结果

5毫克蛋白质/毫升的SHE溶液自身即可增强AHR(p = 0.0033)、增加嗜酸性粒细胞炎症(p = 0.0003)、提高白细胞介素-4、白细胞介素-5、白细胞介素-13、白细胞介素-17A、白细胞介素-17F和CCL20水平,并降低干扰素-γ水平。5毫克蛋白质/毫升的SHE与DEP的组合也会导致AHR和嗜酸性粒细胞炎症增加,但呈现出略有不同的细胞因子谱,Th17相关细胞因子水平更高。然而,虽然3毫克蛋白质/毫升的SHE溶液不会诱发哮喘,但与DEP共同接触会导致AHR(p = 0.002)和嗜酸性粒细胞炎症(p = 0.004)显著增强,白细胞介素-5、白细胞介素-17F和CCL20水平升高,干扰素-γ水平降低。

结论及临床意义

当大豆过敏原浓度过低无法自身引发反应时,大豆过敏原与DEP的组合能够通过Th17相关机制触发哮喘反应。为预防新的哮喘发作,DEP监测可能是过敏原监测的有益补充。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df3a/5476280/007c7a556168/pone.0179569.g001.jpg

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