A mouse model links asthma susceptibility to prenatal exposure to diesel exhaust.
A mouse model links asthma susceptibility to prenatal exposure to diesel exhaust.
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DOI：
10.1016/j.jaci.2013.10.047
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发表时间：
2014-07
影响因子：
14.2
通讯作者：
Gorska, Magdalena M.
中科院分区：
文献类型：
--
作者：
Manners, Sarah;Alam, Rafeul;Schwartz, David A.;Gorska, Magdalena M.
关键词：
大多数哮喘开始于生命的最初几年。这种早期发作不能仅仅归因于遗传因素，因为哮喘的患病率正在增加。流行病学研究表明了产前和幼儿期接触的作用，包括接触柴油机废气。然而，人们对这些机制知之甚少。这主要是由于缺乏动物模型。我们的目的是通过产前暴露于柴油废气来建立哮喘易感性的小鼠模型。对妊娠C57 BL/6雌性小鼠重复鼻内施用柴油机排气颗粒（DEP）或磷酸盐缓冲盐水（PBS）。后代进行次优免疫并用卵清蛋白（OVA）攻击或接受PBS。研究人员检查了幼鼠的哮喘特征，分析了肺和肝组织中DEP调控基因的转录。暴露于DEP的小鼠后代对OVA过敏，表现为气道炎症和高反应性，血清OVA特异性IgE水平升高，肺和全身辅助性T细胞（Th）2和Th 17细胞因子水平升高。这些细胞因子主要由自然杀伤（NK）细胞产生。抗体介导的NK细胞耗竭可预防气道炎症。哮喘易感性与已知受芳香烃受体（AhR）和氧化应激特异性调节的基因转录增加有关。哮喘的特点是边缘或没有在OVA处理的PBS暴露小鼠的幼崽。我们建立了一个小鼠模型，将母亲暴露于DEP与后代的哮喘易感性联系起来。哮喘的发生依赖于NK细胞，并与AhR和氧化应激调节基因的转录增加有关。
Most asthma begins in the first years of life. This early onset cannot be merely attributed to genetic factors, because the prevalence of asthma is increasing. Epidemiological studies have indicated roles for prenatal and early childhood exposures, including exposure to diesel exhaust. However, little is known about the mechanisms. This is largely due to paucity of animal models. We aimed to develop a mouse model of asthma susceptibility through prenatal exposure to diesel exhaust. Pregnant C57BL/6 female mice were given repeated intranasal applications of diesel exhaust particles (DEP) or phosphate-buffered saline (PBS). Offspring underwent suboptimal immunization and challenge with ovalbumin (OVA) or received PBS. Pups were examined for features of asthma; lung and liver tissues were analyzed for transcription of DEP-regulated genes. Offspring of mice exposed to DEP were hypersensitive to OVA, indicated by airway inflammation and hyperresponsiveness, increased serum levels of OVA-specific IgE, and increased levels of pulmonary and systemic T-helper (Th)2 and Th17 cytokines. These cytokines were primarily produced by natural killer (NK) cells. Antibody-mediated depletion of NK cells prevented airway inflammation. Asthma susceptibility was associated with increased transcription of genes known to be specifically regulated by the aryl hydrocarbon receptor (AhR) and oxidative stress. Features of asthma were either marginal or absent in OVA-treated pups of PBS-exposed mice. We created a mouse model that linked maternal exposure to DEP with asthma susceptibility in offspring. Development of asthma was dependent on NK cells and associated with increased transcription from AhR- and oxidative stress-regulated genes.
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DOI：
10.1164/rccm.200402-248oc
发表时间：
2005-02-15
影响因子：
24.7
作者：
Arimoto, T;Kadiiska, MB;Mason, RP
通讯作者：
Mason, RP
影响因子：
14.2
作者：
Ege, MJ;Bieli, C;Braun-Fahrländer, C
通讯作者：
Braun-Fahrländer, C
影响因子：
15.3
作者：
DIXON, FJ;MAURER, PH
通讯作者：
MAURER, PH
DOI：
10.1186/1710-1492-6-7
发表时间：
2010-05-11
期刊：
Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology
影响因子：
--
作者：
Corson L;Zhu H;Quan C;Grunig G;Ballaney M;Jin X;Perera FP;Factor PH;Chen LC;Miller RL
通讯作者：
Miller RL
影响因子：
14.2
作者：
Chang, Ying;Senechal, Stephanie;Tsicopoulos, Anne
通讯作者：
Tsicopoulos, Anne