Ambient ozone, and urban PM_2.5 co-exposure, aggravate allergic asthma via transient receptor potential vanilloid 1-mediated neurogenic inflammation

Highlights

• Co-exposure to PM_2.5 and O₃ induces more severe asthma symptoms than separate exposure.

• Inhibition of TRPV1 has significant anti-inflammatory effects on co-exposure.

• TRPV1 antagonist effectively reduce mucus hyperplasia and AHR on co-exposure.

Abstract

Allergic asthma is the most common pulmonary inflammatory disease, and epidemiological studies have revealed that PM_2.5 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 PM_2.5 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 PM_2.5 and O₃ co-exposure aggravated allergic asthma.