Abstract
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.
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References
Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87(1):245–313
Boothe VL, Boehmer TK, Wendel AM, Yip FY (2014) Residential traffic exposure and childhood leukemia: a systematic review and meta-analysis. Am J Prev Med 46(4):413–422
Brunekreef B, Holgate ST (2002) Air pollution and health. The Lancet 360(9341):1233–1242
Castro-Jiménez MÁ, Orozco-Vargas LC (2011) Parental exposure to carcinogens and risk for childhood acute lymphoblastic leukemia, Colombia, 2000–2005
Crosignani P, Tittarelli A, Borgini A et al (2004) Childhood leukemia and road traffic: a population-based case–control study. Int J Cancer 108(4):596–599
Deng X, Zhang F, Rui W et al (2013) PM2.5-induced oxidative stress triggers autophagy in human lung epithelial A549 cells. Toxicol In Vitro 27(6):1762–1770
Dokter W, Tuyt L, Sierdsema S, Esselink M, Vellenga E (1995) The spontaneous expression of interleukin-1 beta and interleukin-6 is associated with spontaneous expression of AP-1 and NF-kappa B transcription factor in acute myeloblastic leukemia cells. Leukemia 9(3):425–432
Feychting M, Svensson D, Ahlbom A (1998) Exposure to motor vehicle exhaust and childhood cancer. Scand J Work Environ Health 24(1):8–11
Frelin C, Imbert V, Griessinger E et al (2005) Targeting NF-κB activation via pharmacologic inhibition of IKK2-induced apoptosis of human acute myeloid leukemia cells. Blood 105(2):804–811
Giles FJ, Krawczyk J, O’Dwyer M, Swords R, Freeman C (2014) The role of inflammation in leukaemia. Adv Exp Med Biol 816:335–360
Hoek G, Brunekreef B, Goldbohm S, Fischer P, van den Brandt PA (2002) Association between mortality and indicators of traffic-related air pollution in the Netherlands: a cohort study. The Lancet 360(9341):1203–1209
Jin X-T, Song L, Zhao J-Y, Li Z-Y, Zhao M-R, Liu W-P (2014a) Dichlorodiphenyltrichloroethane exposure induces the growth of hepatocellular carcinoma via Wnt/β-catenin pathway. Toxicol Lett 225(1):158–166
Jin X, Chen M, Song L, Li H, Li Z (2014b) The evaluation of p, p′-DDT exposure on cell adhesion of hepatocellular carcinoma. Toxicology 322:99–108
Kim MJ, Nepal S, Lee E-S, Jeong TC, Kim S-H, Park P-H (2013) Ethanol increases matrix metalloproteinase-12 expression via NADPH oxidase-dependent ROS production in macrophages. Toxicol Appl Pharmacol 273(1):77–89
Lee I-T, Yang C-M (2012) Role of NADPH oxidase/ROS in pro-inflammatory mediators-induced airway and pulmonary diseases. Biochem Pharmacol 84(5):581–590
Lee HK, Seo I, Suh DJ, Hong JI, Yoo YH, Park HT (2009) Interleukin-6 is required for the early induction of glial fibrillary acidic protein in Schwann cells during Wallerian degeneration. J Neurochem 108(3):776–786
Leong B, Coombs J, Sabaitis C, Rop D, Aaron C (1998) Quantitative morphometric analysis of pulmonary deposition of aerosol particles inhaled via intratracheal nebulization, intratracheal instillation or nose-only inhalation in rats. J Appl Toxicol 18(2):149–160
Leung P, Wan H, Billah M, Cao J, Ho K, Wong CK (2014) Chemical and biological characterization of air particulate matter 2.5, collected from five cities in China. Environ Pollut 194:188–195
Li R-J, Kou X-J, Geng H, Dong C, Cai Z-W (2014) Pollution characteristics of ambient PM2.5-bound PAHs and NPAHs in a typical winter time period in Taiyuan. Chin Chem Lett 25(5):663–666
Li R, Kou X, Geng H et al (2015) Mitochondrial damage: an important mechanism of ambient PM exposure-induced acute heart injury in rats. J Hazard Mater 287C:392–401
McHale CM, Zhang L, Smith MT (2012) Current understanding of the mechanism of benzene-induced leukemia in humans: implications for risk assessment. Carcinogenesis 33(2):240–252
Miller KA, Siscovick DS, Sheppard L et al (2007) Long-term exposure to air pollution and incidence of cardiovascular events in women. N Engl J Med 356(5):447–458
Murray PJ (2007) The JAK-STAT signaling pathway: input and output integration. J Immunol 178(5):2623–2629
Nam HY, Choi BH, Lee JY et al (2004) The role of nitric oxide in the particulate matter (PM2.5)-induced NFκB activation in lung epithelial cells. Toxicol Lett 148(1):95–102
Pearson RL, Wachtel H, Ebi KL (2000) Distance-weighted traffic density in proximity to a home is a risk factor for leukemia and other childhood cancers. J Air Waste Manag Assoc 50(2):175–180
Peeters PM, Eurlings IM, Perkins TN et al (2014) Silica-induced NLRP3 inflammasome activation in vitro and in rat lungs. Part Fibre Toxicol 11(1):11–58
Pope CA (2001) Particulate air pollution, C-reactive protein, and cardiac risk. Eur Heart J 22(14):1149–1150
Rahman I, MacNee W (1998) Role of transcription factors in inflammatory lung diseases. Thorax 53(7):601–612
Rawlings JS, Rosler KM, Harrison DA (2004) The JAK/STAT signaling pathway. J Cell Sci 117(Pt 8):1281–1283
Riva D, Magalhaes C, Lopes A et al (2011) Low dose of fine particulate matter (PM2.5) can induce acute oxidative stress, inflammation and pulmonary impairment in healthy mice. Inhal Toxicol 23(5):257–267
Rodríguez-Cotto RI, Ortiz-Martínez MG, Rivera-Ramírez E et al (2014) Particle pollution in Rio de Janeiro, Brazil: increase and decrease of pro-inflammatory cytokines IL-6 and IL-8 in human lung cells. Environ Pollut 194:112–120
Samavati L, Rastogi R, Du W, Hüttemann M, Fite A, Franchi L (2009) STAT3 tyrosine phosphorylation is critical for interleukin 1 beta and interleukin-6 production in response to lipopolysaccharide and live bacteria. Mol Immunol 46(8):1867–1877
Shukla A, Timblin C, BeruBe K et al (2000) Inhaled particulate matter causes expression of nuclear factor NF-κB–related genes and oxidant-dependent NF-κ B activation in vitro. Am J Respir Cell Mol Biol 23(2):182–187
Sun SC (2011) Non-canonical NF-kappaB signaling pathway. Cell Res 21(1):71–85
Talbott EO, Xu X, Youk AO, Rager JR, Stragand JA, Malek AM (2011) Risk of leukemia as a result of community exposure to gasoline vapors: a follow-up study. Environ Res 111(4):597–602
Torres-Ramos YD, Montoya-Estrada A, Guzman-Grenfell AM et al (2010) Urban PM2. 5 induces ROS generation and RBC damage in COPD patients. Front Biosci (Elite Ed) 3:808–817
Valavanidis A, Vlachogianni T, Fiotakis K, Loridas S (2013) Pulmonary oxidative stress, inflammation and cancer: respirable particulate matter, fibrous dusts and ozone as major causes of lung carcinogenesis through reactive oxygen species mechanisms. Int J Environ Res Public Health 10(9):3886–3907
Wiemels J (2012) Perspectives on the causes of childhood leukemia. Chem Biol Interact 196(3):59–67
Yang SI (2014) Effect of prenatal exposure to indoor PM2.5 and environmental tobacco smoke affecting lower respiratory tract infection was modified by ROS genes: Cocoa study. In: 2014 AAAAI annual meeting, Aaaai
Ying Z, Xu X, Bai Y et al (2014) Long-term exposure to concentrated ambient PM2.5 increases mouse blood pressure through abnormal activation of the sympathetic nervous system: a role for hypothalamic inflammation. Environ Health Perspect 122(1):79–86
Zhang HY, Zhang Q, Zhang X et al (2011) Cancer-related inflammation and Barrett’s carcinogenesis: interleukin-6 and STAT3 mediate apoptotic resistance in transformed Barrett’s cells. Am J Physiol-Gastrointest Liver Physiol 300(3):G454–G460
Acknowledgments
This work was supported by the National Natural Sciences Foundation of China (Nos. 31271516, 21207084), Zhejiang Province Science Foundation (LY15H280008), The R&D Infrastructure and Facility Development Program of Shanxi Province (2015091015).
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Jin, XT., Chen, ML., Li, RJ. et al. Progression and inflammation of human myeloid leukemia induced by ambient PM2.5 exposure. Arch Toxicol 90, 1929–1938 (2016). https://doi.org/10.1007/s00204-015-1610-x
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DOI: https://doi.org/10.1007/s00204-015-1610-x