Repeated exposure to temperature variation exacerbates airway inflammation through TRPA1 in a mouse model of asthma

Abstract

Background and objective 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. Methods 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. Results 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. Conclusion Repeated exposure to temperature variation exacerbated experimental ‘asthma’ and TRPA1 mediated this temperature‐dependent inflammatory effect.

Cold-induced asthma exacerbation through disruption of murine airway epithelial barrier

“…7D, E, and F). These observations corroborated with those of previous studies, thereby demonstrating that repeated cold exposure could exacerbate asthma in mice (10,11).…”

“…Liao et al suggested that airway in ammation and hyper-responsiveness can be prominently relieved by housing asthmatic mice at a thermoneutral temperature of 30°C, compared with a standard temperature of 20°C (9). Moreover, Deng et al and Du et al showed that repeated cold exposure at 10°C can aggravate asthmatic symptoms in mice (10,11). However, the exact mechanisms underlying the development of asthma under cold conditions remain unclear.…”

Contemporary Concise Review 2019: Asthma

“…The transient receptor potential A1 (TRPA1) has been implicated in both asthma and cough due to cold air . Using an ovalbumin (OVA) model of allergic asthma, researchers demonstrated that repeated exposure to cold air worsened airway inflammation, increased airway hyperreactivity and led to up‐regulation of TRPA1 . Administration of a TRPA1 channel blocker reduced expression and the asthma‐like features that had been seen.…”

TRPA1: A potential target for cold‐induced airway disease?

“…In a recent publication in Respirology, Du et al . use a novel approach of fluctuations in temperature (26/18°C, 26/10°C), in concert with a well‐established, allergen‐induced, aluminium hydroxide/ovalbumin Th2‐driven allergic airways disease model.…”