In utero exposure to second-hand smoke aggravates the response to ovalbumin in adult mice.
In utero exposure to second-hand smoke aggravates the response to ovalbumin in adult mice.
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DOI：
10.1165/rcmb.2013-0164oc
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发表时间：
2013-12
影响因子：
6.4
通讯作者：
R. Xiao;Z. Perveen;R. Rouse;Viviana Le Donne;D. Paulsen;N. Ambalavanan;A. Penn
中科院分区：
文献类型：
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作者：
R. Xiao;Z. Perveen;R. Rouse;Viviana Le Donne;D. Paulsen;N. Ambalavanan;A. Penn
子宫内二手烟（SHS）暴露加剧了成人对环境刺激物的反应。我们测试的假设，在子宫内SHS暴露的影响，调节生理和转录组的反应，在BALB/c小鼠肺卵清蛋白（OVA）的挑战后，延长到成年期，并显示出性别偏见的反应。我们将BALB/c小鼠在子宫内暴露于SHS或过滤空气（AIR），然后用OVA致敏并激发19至23周龄的所有后代。在成人卵清蛋白攻击结束时，我们评估肺功能，检查组织病理学，分析支气管肺泡灌洗液（BALF），并评估肺样本中的基因表达变化。所有组均出现肺部炎症和炎性细胞浸润。肺功能检查（气道高反应性[AHR]、呼吸频率[f]）和BALF（细胞分化，Th 1/Th 2细胞因子）评估显示，SHS-OVA组中的肺应答比AIR-OVA组中的肺应答显著更显著（AHR，f;嗜酸性粒细胞，中性粒细胞; IFN-γ、IL-1b、IL-4、IL-5、IL-10、IL-13、KC/CXCL 1、TNF-α），雄性动物中的大多数应答比雌性动物更明显。子宫内的SHS暴露也显著改变了肺基因表达谱，主要是与炎症反应和呼吸系统疾病相关的基因，包括肺癌和肺纤维化。通过qRT-PCR证实了趋化因子（Cxcl 2、Cxcl 5、Ccl 8、Ccl 24）、细胞因子（Illb、Il 6、Il 13）和急性期应答基因（Saa 1、Saa 3）的改变的表达谱。总之，子宫内暴露于SHS会加剧成人肺部对OVA激发的反应，并促进成人肺部的促哮喘环境;此外，男性通常比女性更容易受到SHS-OVA的影响。
Second-hand smoke (SHS) exposure in utero exacerbates adult responses to environmental irritants. We tested the hypothesis that effects of in utero SHS exposure on modulating physiological and transcriptome responses in BALB/c mouse lungs after ovalbumin (OVA) challenge extend well into adulthood, and that the responses show a sex bias. We exposed BALB/c mice in utero to SHS or filtered air (AIR), then sensitized and challenged all offspring with OVA from 19 to 23 weeks of age. At the end of the adult OVA challenge, we evaluated pulmonary function, examined histopathology, analyzed bronchoalveolar lavage fluid (BALF), and assessed gene expression changes in the lung samples. All groups exhibited lung inflammation and inflammatory cell infiltration. Pulmonary function testing (airway hyperresponsiveness [AHR], breathing frequency [f]) and BALF (cell differentials, Th1/Th2 cytokines) assessments showed significantly more pronounced lung responses in the SHS-OVA groups than in AIR-OVA groups (AHR, f; eosinophils, neutrophils; IFN-γ, IL-1b, IL-4, IL-5, IL-10, IL-13, KC/CXCL1, TNF-α), with the majority of responses being more pronounced in males than in females. SHS exposure in utero also significantly altered lung gene expression profiles, primarily of genes associated with inflammatory responses and respiratory diseases, including lung cancer and lung fibrosis. Altered expression profiles of chemokines (Cxcl2, Cxcl5, Ccl8, Ccl24), cytokines (Il1b, Il6, Il13) and acute phase response genes (Saa1, Saa3) were confirmed by qRT-PCR. In conclusion, in utero exposure to SHS exacerbates adult lung responses to OVA challenge and promotes a pro-asthmatic milieu in adult lungs; further, males are generally more affected by SHS-OVA than are females.