Progression and inflammation of human myeloid leukemia induced by ambient PM2.5 exposure
Progression and inflammation of human myeloid leukemia induced by ambient PM2.5 exposure
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环境 PM2.5 暴露诱发的人类髓系白血病的进展和炎症
DOI：
10.1007/s00204-015-1610-x
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发表时间：
2016-08-01
影响因子：
6.1
通讯作者：
Li, Zhuo-Yu
中科院分区：
文献类型：
--
作者：
Jin, Xiao-Ting;Chen, Mei-Lan;Li, Zhuo-Yu
PM2.5（空气动力学直径2.5 μ m）是一种主要的、普遍存在的空气污染物，已成为全球关注的问题。新出现的证据表明PM2.5与白血病之间存在正相关性，但潜在的分子机制仍不清楚，需要阐明。在这里，我们评估了PM2.5在较低环境剂量下对人类髓系白血病进展和炎症的影响，并探索了可能的途径。我们发现，PM2.5暴露显着诱导白血病细胞的生长，并在体外和体内模型中增加炎症介质的释放。此外，NF-κ B p65和p-STAT 3在PM2.5处理的白血病细胞中被激活，伴随着ROS形成和NADPH氧化酶表达的增加。引人注目的是，包括NAC（ROS）、PDTC（NF-κ B）或WP 1066（STAT 3）在内的抑制剂的补充有助于白血病细胞生长的下降。此外，增加的炎症细胞因子的表达被NAC或PDTC的加入减弱，但不受WP 1066的影响。这项研究表明，PM2.5促进白血病进展，确定了一个潜在的干预目标，并提供了进一步了解PM2.5暴露对人类健康的不利影响。
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.