Prenatal environmental tobacco smoke exposure increases allergic asthma risk with methylation changes in mice.
Prenatal environmental tobacco smoke exposure increases allergic asthma risk with methylation changes in mice.
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DOI：
10.1002/em.22097
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发表时间：
2017-07
影响因子：
2.8
通讯作者：
Cho YH
中科院分区：
文献类型：
--
作者：
Christensen S;Jaffar Z;Cole E;Porter V;Ferrini M;Postma B;Pinkerton KE;Yang M;Kim YJ;Montrose L;Roberts K;Holian A;Cho YH
过敏性哮喘仍然是一种认识不足的疾病。子宫内暴露于环境烟草烟雾（ETS）已被确定为可增加个体哮喘风险的环境暴露。为了提高我们对哮喘发作和发展的理解，我们使用屋尘螨（HDM）过敏原诱导的小鼠模型研究了子宫内ETS暴露对哮喘表型中过敏性疾病易感性的影响。妊娠C57 BL/6小鼠在妊娠期间暴露于过滤空气或ETS，并且它们的后代在6-7周龄时进一步暴露于HDM以诱导过敏性炎症。为了定量DNA甲基化，分析过敏性炎症相关基因和基因组DNA的启动子区域中的甲基化。暴露于HDM导致过敏性肺部炎症的发作，炎症细胞、Th 2细胞因子（IL-4、IL-5和IL-13）和气道重塑的存在增加。当小鼠在子宫内暴露于ETS时，这些哮喘表型显著增强。此外，产前ETS暴露和随后的HDM（ETS/HDM）诱导的哮喘表型与选定的哮喘相关基因（包括IL-4、IL-5、IL-13、Ifn- γ和Foxp 3）的甲基化变化一致。ETS/HDM暴露小鼠的整体DNA甲基化显著低于对照组，这与在肺、脾和血液DNA中观察到的结果一致。产前ETS暴露导致HDM激发后过敏性炎症反应严重增加，并伴有相应的甲基化变化。产前暴露于ETS可能会影响发育可塑性并导致表观遗传编程改变，从而导致哮喘易感性增加。
Allergic asthma remains an inadequately understood disease. In utero exposure to environmental tobacco smoke (ETS) has been identified as an environmental exposure that can increase an individual's asthma risk. To improve our understanding of asthma onset and development, we examined the effect of in utero ETS exposure on allergic disease susceptibility in an asthmatic phenotype using a house dust mite (HDM) allergen-induced murine model. Pregnant C57BL/6 mice were exposed to either filtered air or ETS during gestation, and their offspring were further exposed to HDM at 6-7 weeks old to induce allergic inflammation. To quantify DNA methylation, methylation in the promoter regions of allergic inflammation-related genes and genomic DNA was analyzed. Exposure to HDM resulted in the onset of allergic lung inflammation, with an increased presence of inflammatory cells, Th2 cytokines (IL-4, IL-5, and IL-13), and airway remodeling. These asthmatic phenotypes were significantly enhanced when the mice had been exposed to in utero ETS. Furthermore, prenatal ETS exposure and subsequent HDM (ETS/HDM)-induced asthmatic phenotypes are in agreement with methylation changes in the selected asthma-related genes, including Il-4, Il-5, Il-13, Ifn- γ, and Foxp3. Global DNA methylation was significantly lower in ETS/HDM exposed mice than that of controls, which coincides with the results observed in lung, spleen, and blood DNAs. Prenatal ETS exposure resulted in a severe increase in allergic inflammatory responses after an HDM challenge, with corresponding methylation changes. Prenatal ETS exposure may influence developmental plasticity and result in altered epigenetic programming, leading to an increased susceptibility to asthma.
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影响因子：
100.3
作者：
Huehn, Jochen;Polansky, Julia K.;Hamann, Alf
通讯作者：
Hamann, Alf
影响因子：
3.7
作者：
Karimi, Mohsen;Johansson, Sofia;Ekstrom, Tomas J.
通讯作者：
Ekstrom, Tomas J.
影响因子：
3.7
作者：
Ferrini ME;Simons BJ;Bassett DJ;Bradley MO;Roberts K;Jaffar Z
通讯作者：
Jaffar Z
DOI：
10.1164/rccm.200807-1097oc
发表时间：
2009-04-01
影响因子：
24.7
作者：
Baccarelli, Andrea;Wright, Robert O.;Schwartz, Joel
通讯作者：
Schwartz, Joel
DOI：
10.1165/ajrcmb.20.1.3255
发表时间：
1999-01-01
影响因子：
6.4
作者：
Jaffar, Z;Roberts, K;Holgate, S
通讯作者：
Holgate, S