Ambient ozone, and urban PM2.5 co-exposure, aggravate allergic asthma via transient receptor potential vanilloid 1-mediated neurogenic inflammation

Allergic asthma is the most common pulmonary inflammatory disease, and epidemiological studies have revealed that PM2.5 or ambient ozone (O3) exposure contribute to the higher prevalence of allergic asthma. Current experimental evidence focus principally on the pathogenic effect of exposure to a single air pollutant, ignoring the possible synergistic effect of combined exposure to a mix of these pollutants, which is a more realistic scenario. In this study, allergic mice and a nociceptor antagonist were used to explore the mechanisms of co-exposure to these two important air pollutants. Compared with exposure to either PM2.5 or O3, combined exposure to both greatly aggravated allergic asthma in a dose dependent manner, including increased airway hyperresponsiveness, goblet cell metaplasia, more severe airway inflammation and higher oxidative stress levels. In addition, co-exposure in the allergic mice resulted in elevation of the expression of transient receptor potential vanilloid 1 (TRPV1), and of the production of substance P (SP), which exacerbated lung inflammation by neurogenic inflammation. TRPV1 antagonist (capsazepine, CPZ) treatment for the co-exposed allergic mice, markedly attenuated TRPV1 expression and SP release, and reduced airway inflammation and oxidative damage, further alleviating airway hyperresponsiveness. We conclude that neuro-immune interactions might be involved in PM2.5 and O3 co-exposure aggravated allergic asthma.