Prenatal stress enhances susceptibility of murine adult offspring toward airway inflammation
Prenatal stress enhances susceptibility of murine adult offspring toward airway inflammation
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DOI：
10.4049/jimmunol.177.12.8484
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发表时间：
2006-12-15
影响因子：
4.4
通讯作者：
Arck, Petra C.
中科院分区：
文献类型：
--
作者：
Pincus-Knackstedt, Maike K.;Joachim, Ricarda A.;Arck, Petra C.
过敏性哮喘是发达国家最普遍且持续增长的疾病之一。其临床特征包括气道高反应性和接触过敏原后的炎症。此外，一个新兴的研究领域被纳入胎儿规划，评估子宫内环境损害对以后生活中疾病发病率的影响。这项研究的目的是确定产前暴露在压力下（这是一种严重的环境侮辱）是否会在以后的生活中使气道炎症持续存在。我们在小鼠身上进行的实验显示，产前应激的成年后代确实表现出对气道高反应性和炎症的脆弱性增加。此外，我们提供了有说服力的见解，在产前应激的成年后代中，细胞和体液免疫反应的失调途径，反映在Th2更大的Th1适应性免疫反应和体内CCR3和IgE水平的增加。此外，来自产前应激后代的APCs在体外可触发Th2细胞的克隆扩增。我们还提供了实验证据，证明成年后代室旁核中的促肾上腺皮质激素释放激素表达在产前应激反应中降低。此外，行为分析表明，这些小鼠的焦虑情绪有所增加。总之，我们的数据将促进未来的研究，旨在确定跨学科背景下气道炎症中多个关键因素的个体影响、层次结构和冗余。这将有助于在产前制定预防疾病战略，例如哮喘。
Allergic asthma is one of the most prevalent and continuously increasing diseases in developed countries. Its clinical features include airway hyperresponsiveness and inflammation upon allergen contact. Furthermore, an emerging area of research subsumed as fetal programming evaluates the impact of environmental insults in utero on the incidence of diseases in later life. The aim of this study was to identify whether prenatal exposure to stress, which constitutes a severe environmental insult, perpetuates airway inflammation in later life. Our experiments were performed in mice and revealed that prenatally stressed adult offspring indeed show an increased vulnerability toward airway hyperresponsiveness and inflammation. Furthermore, we provide persuasive insights on dysregulated pathways of the cellular and humoral immune response upon Ag challenge in prenatally stressed adult offspring, reflected by a Th2 greater Th1 adaptive immune response and increased CCR3 and IgE levels in vivo. Additionally, APCs derived from prenatally stressed offspring trigger clonal expansion of Th2 cells in vitro. We also deliver experimental evidence for a reduced corticotrophin-releasing hormone expression in the paraventricular nucleus of adult offspring in response to prenatal stress. Furthermore, behavioral analyses indicate an increase in anxiety in these mice. In conclusion, our data will facilitate future research aiming to identify the individual impact, hierarchy, and redundancy of multiple key protagonists in airway inflammation in an interdisciplinary context. This will foster the substantiation of disease-prevention strategies, such as asthma, during the prenatal period.