Continuous exposure of PM2.5 exacerbates ovalbumin-induced asthma in mouse lung via a JAK-STAT6 signaling pathway
Yonghui Yang, Xiaoxia Li, Xiaoying An, Ling Zhang, X Y Li, Liang Wang, Guiyun Zhu
Abstract
BACKGROUND: Epidemiological studies and mice models have demonstrated that air pollution containing particulate matter smaller than 2.5 μm (PM2.5) exacerbates acute episodes of asthma in both children and adults. OBJECTIVES: To investigate the effect of continuous PM2.5 treatment on asthma regulation mechanism behind this effect. MATERIAL AND METHODS: In this study, the effects of continuous exposure to PM2.5 on asthma and eosinophil recruitment was compared to the effect of a single pre-ovalbumin (OVA)-sensitization exposure to PM2.5. Wild-type mice were either challenged once with PM2.5 + OVA before sensitization and asthma induction over a 27-day period, or with 5 times of PM2.5 + OVA treatment and sensitization/asthma induction over the same period. RESULTS: Continuous exposure to PM2.5 significantly increased total plasma immunoglobulin E (IgE), bronchial alveolar lavage fluid (BALF) cell numbers, eosinophils, and macrophages, leading to increased lung injury. This effect was regulated through increased production of chemokines and cytokines, such as interleukin (IL)-1β, monocyte chemoattractant protein 1 (MCP-1), IL-12, IL-5, IL-13, and prostaglandin D2 (PGD2). Eosinophil recruitment during continuous PM2.5 treatment was regulated through phosphorylation of the JAK/STAT6 pathway. As this study shows, continuous PM2.5 treatment significantly worsens asthma as compared to single exposure to PM2.5 or OVA exposure alone. CONCLUSIONS: Our findings reveal that continuous exposure of PM2.5 exacerbates OVA-induced asthma in mouse lung through JAK-STAT6 signaling pathway.