Progression and inflammation of human myeloid leukemia induced by ambient PM2.5 exposure.
PM2.5 (aerodynamic diameter ≤2.5 μm) 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-κB 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-κB), 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.
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China.
Xiao-Ting
XT
Jin
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China.
Mei-Lan
ML
Chen
Institute of Environmental Science, Shanxi University, Taiyuan, China.
Rui-Jin
RJ
Li
China Institute for Radiation Protection, Taiyuan, China.
Quan
Q
An
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China.
Li
L
Song
Biology Institute of Shanxi, Taiyuan, China.
Yi
Y
Zhao
Department of Pathology, Shanxi Medical University, Taiyuan, China.
Hong
H
Xiao
Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. lcheng@enders.tch.harvard.edu.
Long
L
Cheng
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China. lzy@sxu.edu.cn.|College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China. lzy@sxu.edu.cn.
Zhuo-Yu
ZY
Li
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007942:Leukemia, Experimental / Q000276:immunology* / Q000473:pathology; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D052638:Particulate Matter / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
D000393:Air Pollutants; D016207:Cytokines; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051996:Transcription Factor RelA
Inflammation; Leukemia; PM2.5; Progression; ROS