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/m(3) and 35 μg/m(3)), 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/m(3) 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/m(3)) 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).