Oxidative stress-mediated epidermal growth factor receptor activation regulates PM-induced over-secretion of pro-inflammatory mediators from human bronchial epithelial cells.

BACKGROUND

Exposure to PM has been associated with increased morbidity and mortality of lung diseases although the underlying mechanisms have not been fully uncovered. Airway inflammation is a critical event in the pathogenesis of lung diseases. This study aimed to examine the role of oxidative stress and epidermal growth factor receptor (EGFR) in PM-induced pro-inflammatory response in a human bronchial epithelial cell line, BEAS-2B.

METHODS

BEAS-2B cells were exposed to 0, 20, 50, 100 and 150 μg/ml of PM. Secretion of pro-inflammatory mediators including interleukin-6 (IL-6), IL-8 and IL-1β was determined using enzyme linked immunosorbent assay. Levels of intracellular reactive oxygen species (ROS) were determined using flow cytometry. Phosphorylation of the EGFR was examined with immunoblotting.

RESULTS

PM exposure increased the secretion of IL-6, IL-8, and IL-1β in a concentration-dependent fashion. Moreover, exposure to PM elevated intracellular levels of ROS, and phosphorylation of the EGFR (Y1068). Pretreatment of BEAS-2B cells with either an antioxidant or a specific EGFR inhibitor significantly reduced PM-induced IL-6, IL-8 and IL-1β secretion, implying that both oxidative stress and EGFR activation were involved in PM-induced pro-inflammatory response. Furthermore, pre-treatment of BEAS-2B cells with an antioxidant significantly blunted PM-induced EGFR activation, suggesting that oxidative stress was required for PM-induced EGFR activation.

CONCLUSION

PM exposure induces pro-inflammatory response in human bronchial epithelial cells through oxidative stress-mediated EGFR activation.