Progression and inflammation of human myeloid leukemia induced by ambient PM2.5 exposure

摘要

PM2.5 (aerodynamic diameter a parts per thousand currency sign2.5 mu m) has been a dominating and ubiquitous air pollutant and has become a global concern. Emerging evidences suggest a positive correlation between PM2.5 and leukemia, but the underlying molecular mechanisms remain unclear and need to be elucidated. Here, we assessed the impacts of PM2.5 on the progression and inflammation of human myeloid leukemia at lower environmental doses and explored the possible pathway. We showed that PM2.5 exposure significantly induced the leukemia cell growth and enhanced the release of inflammatory mediators in both in vitro and in vivo models. Additionally, NF-kappa B p65 and p-STAT3 were activated in PM2.5-treated leukemia cells, with a concomitant increase in both ROS formation and NADPH oxidase expressions. Strikingly, the supplement of inhibitors, including NAC (ROS), PDTC (NF-kappa B), or WP1066 (STAT3), contributed to a decline in leukemia cell growth. Furthermore, enhanced expressions of inflammatory cytokines were attenuated by the addition of NAC or PDTC, but not affected by WP1066. This study demonstrates that PM2.5 promotes leukemia progression, identifies a potential intervention target, and provides further understanding of the detrimental effect of PM2.5 exposure on human health.