Joint International Research Laboratory of Green Buildings and Built Environments (Ministry of Education), Chongqing University, Chongqing, China.
National Centre for International Research of Low-Carbon and Green Buildings (Ministry of Science and Technology), Chongqing University, Chongqing, China.
Respirology. 2019 Mar;24(3):238-245. doi: 10.1111/resp.13433. Epub 2018 Nov 15.
Studies from epidemiology suggest that ambient temperature is one of the underlying triggers and potential causes of asthma. The aim of this study was to examine the impact and the molecular mechanism of temperature-invoked airway inflammation using an experimental model of asthma in BALB/c mice.
Mice were exposed to different temperature conditions (steady 26°C, 26°C/18°C cycle, 26°C/10°C cycle) and received sensitization and challenge of ovalbumin (OVA) during a 21-day period. HC030031, a selective transient receptor potential A1 (TRPA1) channel blocker, was used to investigate the underlying mechanism of TRPA1 in 'asthmatic' airways. After the final OVA challenge, in vivo lung function was measured, and bronchoalveolar lavage fluid (BALF) and pulmonary inflammation were assessed.
The temperature variations, especially the largest temperature difference (16°C), exacerbated airway inflammation in OVA-induced mice, increasing the levels of serum total-IgE (immunoglobulin E) and IgG1, inflammatory cells and cytokines in BALF. Analysis of histopathological changes and lung function verified that repeated exposure to very cold and changed temperatures aggravated airway hyperresponsiveness (AHR). Significant upregulation of TRPA1 expression was revealed by immunohistochemistry in the presence of the largest temperature variation (26°C/10°C cycle), while administration of HC030031 successfully inhibited TRPA1 expression, thus attenuating the asthma-like pathological features.
Repeated exposure to temperature variation exacerbated experimental 'asthma' and TRPA1 mediated this temperature-dependent inflammatory effect.
流行病学研究表明，环境温度是哮喘的潜在触发因素和潜在原因之一。本研究旨在使用 BALB/c 小鼠哮喘实验模型研究温度诱发的气道炎症的影响和分子机制。
小鼠暴露于不同温度条件（稳定 26°C、26°C/18°C 循环、26°C/10°C 循环），并在 21 天期间接受卵清蛋白（OVA）致敏和激发。使用选择性瞬时受体电位 A1（TRPA1）通道阻滞剂 HC030031 来研究 TRPA1 在“哮喘”气道中的潜在机制。在最后一次 OVA 挑战后，测量体内肺功能，并评估支气管肺泡灌洗液（BALF）和肺部炎症。
温度变化，特别是最大温差（16°C），加剧了 OVA 诱导的小鼠气道炎症，增加了血清总 IgE（免疫球蛋白 E）和 IgG1、BALF 中的炎症细胞和细胞因子水平。组织病理学变化和肺功能分析证实，反复暴露于极冷和变化的温度会加重气道高反应性（AHR）。最大温度变化（26°C/10°C 循环）存在时，免疫组织化学显示 TRPA1 表达明显上调，而 HC030031 的给药成功抑制了 TRPA1 表达，从而减轻了类似哮喘的病理特征。
反复暴露于温度变化会加重实验性“哮喘”，而 TRPA1 介导了这种温度依赖性炎症效应。
