Atmospheric particulate matter with a diameter ≤2.5 μm (PM2.5) can induce inflammation of the respiratory system, which is the pathological basis of asthma or other respiratory diseases; however, the underlying regulation mechanism has not been clearly addressed. The aim of this study was to explore the potential role of the oxidative stress-JAK/STAT signaling pathway in the inflammation of human bronchial epithelial cells induced by PM2.5. The human bronchial epithelial cell line 16HBE cells were stimulated with PM2.5 at 50 and 100 μg/mL doses for 12 or 24 hours. Intracellular reactive oxygen species (ROS) was detected using flow cytometry. Gene and protein expressions of JAK2, STAT3 and cyclooxygenase 2 (COX-2) were determined using reverse transcription-polymerase chain reaction and western blotting, respectively. The ratio of intracellular glutathione/glutathione disulfide (GSH/GSSG) and the levels of interleukin (IL)-6 and IL-8 in cellular supernatant were analyzed using enzyme-linked immunosorbent assay. The results indicated that PM2.5 treatment significantly increased gene expressions of JAK2/STAT3 and protein levels of p-JAK2/p-STAT3, accompanied by increased intracellular ROS levels, decreased GSH/GSSG ratio at 50 and 100 μg/mL of PM2.5, and significantly enhanced levels of IL-6, IL-8 and COX-2 at a dose of 100 μg/mL. Pretreatment with N-acetyl-l-cysteine (NAC) attenuated the oxidative stress induced by PM2.5; similarly, pretreatment with AG490 (an inhibitor of JAK) decreased the cytokine levels stimulated by PM2.5. Therefore, we concluded that PM2.5 exposure could activate oxidative stress-JAK2/STAT3 signaling pathway, elevate the levels of IL-6, IL-8 and COX-2 in 16HBE cells, which can be inhibited by the NAC or AG490.
Keywords: COX-2; IL-6; IL-8; JAK/STAT; PM2.5; oxidative stress.
© 2020 John Wiley & Sons, Ltd.