PM 2 . 5 exacerbate allergic asthma involved in autophagy signaling pathway in mice

Epidemiological studies indicate an association between high levels of ambient particulate matter and increased incidence of asthma disorders. Asthmatics experience a physiologic airway disturbance, many forms of which are caused by chronic airway inflammatory processes. We previously demonstrated that particulate matter 2.5 (PM2.5) toxicology induces autophagy via inhibition of the PI3K/Akt/mTOR-kinase signaling pathway in human bronchial epithelial cells. PM2.5 also exacerbates asthma in a murine model of allergen-induced asthma, but its mechanism remains elusive. We used a mouse model (6-8 week-old SPF female BALB/c mouse sensitized with Ovalbumin (OVA)) to investigate the effect of PM2.5 on allergic inflammatory asthma. We evaluated PM2.5-induced inflammation and bronchial hyperreactivity and analyzed the correlation between these factors and autophagy. Mice were sensitized at day 1, 8, 15 and challenged at day 16, 19, 22 with OVA or OVA+PM2.5 or PM2.5 only. Mice were sacrificed one day following the last OVA challenge. Bronchial hyperreactivity was assessed with methacholine. Levels of inflammatory cytokines were measured by enzyme-linked immuno sorbent assay (ELISA) or real-time quantitative PCR (QPCR) respectively. The expression of autophagy genes was detected by RT-qPCR or western blot; LC3-positive vesicles were revealed by immunofluorescence microscopy. We found that the total number of cells and the number of eosinophils, neutrophils and macrophages from bronchial alveolar lavage fluid (BALF) in the OVA-sensitization/OVA + PM2.5-challenge (AP) group were significantly higher than in the control (NC) group and OVA-sensitization + OVA-challenge (AC) group. We observed some correlation between autophagy and inflammatory factors in the PM2.5-exacerbated mouse asthma model. Our data demonstrated that elevated inflammatory levels were strongly associated with reduced autophagy related factors in the OVA/PM2.5-exacerbated mouse allergic inflammatory asthma model. PM2.5 exacerbated inflammation and decreased autophagy in this mouse allergic inflammatory asthma model. However, PM2.5 alone did not along trigger asthmatic responses in the absence of concurrent OVA challenge. The present findings support the role of PM2.5 in augmenting allergic inflammatory asthma.