Ambient particulate matter-associated autophagy alleviates pulmonary inflammation induced by Platanus pollen protein 3 (Pla3)

Abstract

Subpollen particles (SPPs) with diameter less than 1 mm released from allergenic pollen grains contain allergens could trigger asthma and lung inflammation after being inhaled. In the meaning time, ambient fine particles attached on the pollen grains could have further effects on the inflammation. However, the mechanisms underlying these phenomena have not been fully elucidated. In this study, the effects of autophagy triggered by PM2.5 and Platanus SPPs were evaluated by using the A549 cell lines and a pollen sensitized rat model. First, autophagy in A549 cells was analyzed after exposure to PM2.5 using acridine orange staining, real-time quantitative PCR (qRT-PCR), and western blot (WB) assays. The increased levels of ROS, superoxide dismutase, and malonaldehyde in the lung homogenates of rats exposed to SPPs indicated that inflammatory response was triggered in the lungs. Treatment with autophagy-inhibiting drugs showed that autophagy suppressed ROS formation and decreased the production of thymic stromal lymphopoietin (TSLP), a critical pathway altering the inflammatory response. Although the effect was indirect, autophagy appeared to negatively regulate TSLP levels, resulting in a compromised immune response. These results suggested that SPPs promote ROS generation and increase TSLP levels, triggering downstream inflammation reactions. However, ambient PM2.5 could aggravate autophagy, which in turn effectively suppressed ROS and TSLP levels, leading to the alleviation of the immune response and pulmonary inflammation.