Airway exposure to perfluorooctanoate exacerbates airway hyperresponsiveness and downregulates glucocorticoid receptor expression in asthmatic mice.
Airway exposure to perfluorooctanoate exacerbates airway hyperresponsiveness and downregulates glucocorticoid receptor expression in asthmatic mice.
复制标题
哮喘小鼠气道暴露于全氟辛酸酯可加重气道高反应性并下调糖皮质激素受体表达。
DOI：
10.21037/tp-20-246
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发表时间：
2021-03
影响因子：
2
通讯作者：
Dong X
中科院分区：
文献类型：
--
作者：
Zeng Z;Ma W;Zhao R;Dong X
多种环境危险因素在哮喘的发病机制中发挥着至关重要的作用，从而导致哮喘的表型表达。全氟辛酸 (PFOA) 是人类中最常见、最丰富的全氟化碳 (PFC)，已在全世界的水和大气中检测到。糖皮质激素受体（GR）被认为对哮喘具有保护作用，并且与糖皮质激素的敏感性有关。经皮或口腔接触 PFOA 已被证明会对卵清蛋白 (OVA) 诱发哮喘患者的气道炎症产生多种影响。值得注意的是，气道暴露对哮喘的发病机制具有关键作用。然而，目前尚不清楚气道暴露于 PFOA 对哮喘患者气道高反应性 (AHR) 的影响。 BALB/c 小鼠接受 OVA 诱导哮喘。然后将 PFOA 气管内给予 OVA 诱导的小鼠 7 天。然后我们评估了气道暴露于 PFOA 对哮喘小鼠 AHR 的影响以及 GR 表达的调节。结果显示，哮喘小鼠的 AHR 和 2 型辅助性 T (Th2) 气道炎症加剧。此外，这些小鼠的 GR mRNA 和蛋白质表达显着下降。这些数据强烈表明，急性气道暴露于PFOA会导致Th2相关的AHR并降低GR表达，这可能会增加哮喘治疗的难度。
Multiple environmental risk factors play a vital role in the pathogenesis of asthma, which contribute to the phenotypic expression of asthma. Perfluorooctanoate (PFOA) is the most common and abundant perfluorocarbon (PFC) in humans, and it has been detected in water and the atmosphere worldwide. Glucocorticoid receptor (GR) is considered to exert a protective effect on asthma and is associated with the sensitivity to glucocorticoids. Dermal or oral exposure to PFOA has been shown to contribute various effects on airway inflammation in individuals with ovalbumin (OVA)-induced asthma. Notably, airway exposure has a critical contribution to the pathogenesis of asthma. However, the effect of airway exposure to PFOA on airway hyperresponsiveness (AHR) in patients with asthma is not currently understood. BALB/c mice were administered OVA to induce asthma. PFOA was then administered intratracheally to OVA-induced mice for seven days. Then we assessed the effect of airway exposure to PFOA on AHR and the regulation of the GR expression in asthmatic mice. The results showed aggravated AHR and T helper type 2 (Th2) airway inflammation in asthmatic mice. Furthermore, these mice show a substantial decrease in the expression of the GR mRNA and protein. These data strongly suggest that acute airway exposure to PFOA leads to Th2-related AHR and decreases GR expression, which may increase the difficulty in the treatment of asthma.