Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan 430079, Hubei, China.
Joint International Research Laboratory of Green Buildings and Built Environments (Ministry of Education), Chongqing University, Chongqing 400045, China.
Environ Pollut. 2020 Jan;256:113375. doi: 10.1016/j.envpol.2019.113375. Epub 2019 Oct 16.
Some studies have indicated that formaldehyde, a ubiquitous environmental pollutant, can induce or aggravate allergic asthma. Epidemiological studies have also shown that the relative humidity indoors may be an independent and a key factor associated with the aggravation of allergic asthma. However, the synergy of humidity and formaldehyde on allergic asthma and the mechanism underlying this effect remain largely unknown. In this study, we aim to determine the effect of high relative humidity and/or formaldehyde exposure on allergic asthma and explore the underlying mechanisms. Male Balb/c mice were modeled with ovalbumin (OVA) and exposure to 0.5 mg/m formaldehyde and/or different relative humidity (60%/75%/90%). Histopathological changes, pulmonary function, Th1/Th2 balance, the status of mucus hypersecretion and the levels of inflammatory factors were detected to assess the exacerbation of allergic asthma. The levels of the transient receptor potential vanilloid 4 (TRPV4), calcium ion and the activation of p38 mitogen-activated protein kinases (p38 MAPK) were detected to explore the underlying mechanisms. The results showed that exposure to high relative humidity or to 0.5 mg/m formaldehyde alone had a slight, but not significant, affect on allergic asthma. However, the pathological response and airway hyperresponsiveness (AHR) were greatly aggravated by simultaneous exposure to 0.5 mg/m formaldehyde and 90% relative humidity. Blocking TRPV4or p38 MAPK using HC-067047 and SB203580 respectively, effectively alleviated the exacerbation of allergic asthma induced by this simultaneous exposure to formaldehyde and high relative humidity. The results show that when formaldehyde and high relative humidity are present this can enhance the activation of the TRPV4 ion channel in the lung leading to the aggravation of the p38 MAPK activation, resulting in the exacerbation of inflammation and hypersecretion of mucus in the airways.
一些研究表明，甲醛作为一种普遍存在的环境污染物，可能会诱发或加重过敏性哮喘。流行病学研究还表明，室内相对湿度可能是与过敏性哮喘加重相关的一个独立且关键的因素。然而，高湿度和甲醛对过敏性哮喘的协同作用及其潜在机制仍知之甚少。在这项研究中，我们旨在确定高相对湿度和/或甲醛暴露对过敏性哮喘的影响，并探讨其潜在机制。我们使用卵清蛋白（OVA）对雄性 Balb/c 小鼠进行建模，并使其暴露于 0.5mg/m3 的甲醛和/或不同的相对湿度（60%/75%/90%）。通过检测组织病理学变化、肺功能、Th1/Th2 平衡、黏液高分泌状态和炎症因子水平，评估过敏性哮喘的加重情况。检测瞬时受体电位香草醛 4（TRPV4）、钙离子和丝裂原活化蛋白激酶 p38（p38 MAPK）的激活水平，以探讨潜在机制。结果表明，单独暴露于高相对湿度或 0.5mg/m3 甲醛对过敏性哮喘的影响较小，但不显著。然而，同时暴露于 0.5mg/m3 甲醛和 90%相对湿度会大大加重病理反应和气道高反应性（AHR）。分别使用 HC-067047 和 SB203580 阻断 TRPV4 或 p38 MAPK，可有效缓解甲醛和高相对湿度同时暴露引起的过敏性哮喘加重。结果表明，当甲醛和高相对湿度同时存在时，会增强肺中 TRPV4 离子通道的激活，从而加重 p38 MAPK 的激活，导致炎症和气道黏液高分泌加重。
