Zeng Zeyu, Ma Weihui, Zhao Ran, Dong Xiaoyan
Department of Respiratory Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Transl Pediatr. 2021 Feb;10(2):323-332. doi: 10.21037/tp-20-246.
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.
多种环境风险因素在哮喘发病机制中起关键作用，这些因素促成了哮喘的表型表达。全氟辛酸（PFOA）是人类体内最常见且含量丰富的全氟化碳（PFC），已在全球范围内的水和大气中被检测到。糖皮质激素受体（GR）被认为对哮喘具有保护作用，且与对糖皮质激素的敏感性相关。皮肤或口服接触PFOA已被证明会对卵清蛋白（OVA）诱导的哮喘个体的气道炎症产生多种影响。值得注意的是，气道暴露对哮喘发病机制有重要影响。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。
给BALB/c小鼠注射OVA以诱导哮喘。然后对OVA诱导的小鼠进行气管内注射PFOA，持续7天。接着我们评估气道暴露于PFOA对哮喘小鼠AHR的影响以及GR表达的调节情况。
结果显示哮喘小鼠的AHR加重，2型辅助性T细胞（Th2）气道炎症加剧。此外，这些小鼠的GR mRNA和蛋白表达大幅下降。
这些数据有力地表明，急性气道暴露于PFOA会导致与Th2相关的AHR，并降低GR表达，这可能会增加哮喘治疗的难度。
