The Synergistic Effects of Fine Particulate Matter and High Humidity on Allergic Asthma: An Association with TRPV4/MAPK Pathway Activation

Identifying environmental factors contributing to allergic asthma is critical for effective prevention. PM_2.5, a major environmental pollutant, and high relative humidity frequently coexist in urban and industrialized regions, particularly when ventilation is poor. However, the combined effects of PM_2.5 and humidity remain unclear. This study used a murine asthma model, exposing male Balb/c mice sensitized with ovalbumin (OVA) to PM_2.5 (75 μg/m³ and 35 μg/m³), based on China's Ambient Air Quality Standards (GB3095-2012), and/or varying relative humidity levels in a controlled chamber. Allergic asthma severity was evaluated through histopathological changes, pulmonary function, Th1/Th2 balance, mucus hypersecretion, and inflammatory factor levels, alongside the activation of TRPV4 and MAPK signaling pathways (ERK, p38MAPK, and JNK). The results showed that high humidity (90%) or PM_2.5 exposure alone had minimal impact, but combined exposure to 75 μg/m³ PM_2.5 and 90% humidity markedly aggravated airway hyperresponsiveness, inflammation, and mucus hypersecretion. These changes coincided with enhanced TRPV4 activation and MAPK signaling, particularly p38MAPK and JNK, while ERK1/2 remained unaffected. A lower PM_2.5 concentration (35 μg/m³) combined with 90% humidity had a weaker impact. Blocking TRPV4 with HC-067047 effectively mitigated asthma exacerbation caused by combined exposure. These findings demonstrate that co-exposure to PM_2.5 and high humidity dose-dependently exacerbates allergic asthma, an effect likely mediated by TRPV4-MAPK pathway activation. Targeting TRPV4 may offer a potential therapeutic strategy to mitigate asthma exacerbation in environments with high humidity and PM_2.5.