1.Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing 100071, China
2.Beijing Key Laboratory of Bioactive Substances and Functional Foods, Beijing Union University, Beijing 100191, China
*: xiaohong@buu.edu.cn
纸质出版:2017-12
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PM2.5 obtained from urban areas in Beijing induces apoptosis by activating nuclear factor-kappa B[J]. MMR, 2017,4(4):200-209.
Peng et al.: PM2.5 obtained from urban areas in Beijing induces apoptosis by activating nuclear factor-kappa B. Mil Med Res, 2017, 4: 27
PM2.5 obtained from urban areas in Beijing induces apoptosis by activating nuclear factor-kappa B[J]. MMR, 2017,4(4):200-209. DOI: 10.1186/s40779-017-0136-3.
Peng et al.: PM2.5 obtained from urban areas in Beijing induces apoptosis by activating nuclear factor-kappa B. Mil Med Res, 2017, 4: 27 DOI: 10.1186/s40779-017-0136-3.
Background:
2
Particulate matter (PM)
which has adverse effects on citizen health
is a major air pollutant in Beijing city. PM
2.5
is an indicator of PM in urban areas and can cause serious damage to human health. Many epidemiological studies have shown that nuclear factor-kappa B (NF-κB) is involved in PM
2.5
-induced cell injury
but the exact mechanisms are not well understood.
Methods:
2
The cytotoxic effects of PM
2.5
at 25–1600μg/ml for 24h were determined by MTT assay in Chinese hamster ovary cells (CHO) cells. Flow cytometry was used to determine the apoptosis rate induced by PM
2.5
. The destabilized enhanced green fluorescent protein (d2EGFP) green fluorescent protein reporter system was used to determine the NF-κB activity induced by PM
2.5
. The expression of pro-apoptotic Bcl-2-associated death promoter (BAD) proteins induced by PM
2.5
was determined by Western blotting to explore the relationship between PM
2.5
and the NF-κB signaling pathway and to determine the toxicological mechanisms of PM
2.5
.
Results:
2
PM
2.5
collected in Beijing urban districts induces cytotoxic effects in CHO cells according to MTT assay with 72.28% cell viability rates even at 200μg/ml PM
2.5
and flow cytometry assays with 26.97% apoptosis rates at 200μg/ml PM
2.5
. PM
2.5
increases the activation levels of NF-κB
which have maintained for 24h. 200μg/ml PM
2.5
cause activation of NF-κB after exposure for 4h
the activation peak appears after 13.5h with a peak value of 25.41%. The average percentage of NF-κB activation in whole 24h is up to 12.90% by 200μg/ml PM
2.5
. In addition
PM
2.5
decreases the expression level of the pro-apoptotic protein BAD in a concentration-dependent manner.
Conclusion:
2
PM
2.5
induces NF-κB activation
which persists for 24h. The expression of pro-apoptotic protein BAD decreased with increased concentrations of PM
2.5
. These findings suggest that PM
2.5
plays a major role in apoptosis by activating the NF-κB signaling pathway and reducing BAD protein expression.
Wong CM , Thach TQ , Chau PY , Chan EK , Chung RY , Ou CQ , et al . Part 4. Interaction between air pollution and respiratory viruses: time-series study of daily mortality and hospital admissions in Hong Kong . Res Rep Health Eff Inst . 2010 ; 154 : 283 - 362 .
Kelly FJ , Fussell JC . Air pollution and airway disease . Clin Exp Allergy . 2011 ; 41 : 1059 - 71 .
Sacks JD , Stanek LW , Luben TJ , Johns DO , Buckley BJ , Brown JS , et al . Particulate matter-induced health effects: who is susceptible? Environ Health Perspect . 2011 ; 119 : 446 - 54 .
Kim SY , Sheppard L , Kaufman JD , Bergen S , Szpiro AA , Larson TV , et al . Individual-level concentrations of fine particulate matter chemical components and subclinical atherosclerosis: a cross-sectional analysis based on 2 advanced exposure prediction models in the multi-ethnic study of atherosclerosis . Am J Epidemiol . 2014 ; 180 : 718 - 28 .
Sarigiannis D , Karakitsios SP , Zikopoulos D , Nikolaki S , Kermenidou M . Lung cancer risk from PAHs emitted from biomass combustion . Environ Res . 2015 ; 137 : 147 - 56 .
Atkinson RW , Kang S , Anderson HR , Mills IC , Walton HA . Epidemiological time series studies of PM2.5 and daily mortality and hospital admissions: a systematic review and meta-analysis . Thorax . 2014 ; 69 : 660 - 5 .
Grahame TJ , Klemm R , Schlesinger RB . Public health and components of particulate matter: the changing assessment of black carbon . J Air Waste Manag Assoc . 2014 ; 64 : 620 - 60 .
Karottki DG , Beko G , Clausen G , Madsen AM , Andersen ZJ , Massling A , et al . Cardiovascular and lung function in relation to outdoor and indoor exposure to fine and ultrafine particulate matter in middle-aged subjects . Environ Int . 2014 ; 73 : 372 - 81 .
Organization WH . Air quality guidelines: Global update 2005: Particulate matter, ozone, nitrogen dioxide and sulfur dioxide . Indian J Med Res . 2006 ; 4 : 492 - 3 .
Wu J , Li J , Peng J , Li W , Xu G , Dong C . Applying land use regression model to estimate spatial variation of PM 2.5 in Beijing, China . Environ Sci Pollut Res Int . 2015 ; 22 : 7045 - 61 .
Burnett RT , Pope CA 3rd , Ezzati M , Olives C , Lim SS , Mehta S , et al . An integrated risk function for estimating the global burden of disease attributable to ambient fine particulate matter exposure . Environ Health Perspect . 2014 ; 122 : 397 - 403 .
Tsai SS , Chiu HF , Liou SH , Yang CY . Short-term effects of fine particulate air pollution on hospital admissions for respiratory diseases: a case-crossover study in a tropical city . J Toxicol Environ Health A . 2014 ; 77 : 1091 - 101 .
Zhou B , Liang G , Qin H , Peng X , Huang J , Li Q , et al . p53-dependent apoptosis induced in human bronchial epithelial (16-HBE) cells by PM(2.5) sampled from air in Guangzhou, China . Toxicol Mech Methods . 2014 ; 24 : 552 - 9 .
Liu Y , Chen YY , Cao JY , Tao FB , Zhu XX , Yao CJ , et al . Oxidative stress, apoptosis, and cell cycle arrest are induced in primary fetal alveolar type II epithelial cells exposed to fine particulate matter from cooking oil fumes . Environ Sci Pollut Res Int . 2015 ; 22 : 9728 - 41 .
Niederberger E , Geisslinger G . Proteomics and NF-kappaB: an update . Expert Rev Proteomics . 2013 ; 10 : 189 - 204 .
Jing H , Lee S . NF-kappaB in cellular senescence and cancer treatment . Mol Cells . 2014 ; 37 : 189 - 95 .
Nguyen DP , Li J , Yadav SS , Tewari AK . Recent insights into NF-kappaB signalling pathways and the link between inflammation and prostate cancer . BJU Int . 2014 ; 114 : 168 - 76 .
Shukla A , Timblin C , BeruBe K , Gordon T , McKinney W , Driscoll K , et al . Inhaled particulate matter causes expression of nuclear factor (NF)-kappaBrelated genes and oxidant-dependent NF-kappaB activation in vitro . Am J Respir Cell Mol Biol . 2000 ; 23 : 182 - 7 .
Dagher Z , Garcon G , Billet S , Verdin A , Ledoux F , Courcot D , et al . Role of nuclear factor-kappa B activation in the adverse effects induced by air pollution particulate matter (PM2.5) in human epithelial lung cells (L132) in culture . J Appl Toxicol . 2007 ; 27 : 284 - 90 .
Everhart MB , Han W , Sherrill TP , Arutiunov M , Polosukhin VV , Burke JR , et al . Duration and intensity of NF-kappaB activity determine the severity of endotoxin-induced acute lung injury . J Immunol . 2006 ; 176 : 4995 - 5005 .
Tang X , Liu D , Shishodia S , Ozburn N , Behrens C , Lee JJ , et al . Nuclear factor-kappaB (NF-kappaB) is frequently expressed in lung cancer and preneoplastic lesions . Cancer . 2006 ; 107 : 2637 - 46 .
Lin CC , Chiang LL , Lin CH , Shih CH , Liao YT , Hsu MJ , et al . Transforming growth factor-beta1 stimulates heme oxygenase-1 expression via the PI3K/Akt and NF-kappaB pathways in human lung epithelial cells . Eur J Pharmacol . 2007 ; 560 : 101 - 9 .
Shi J , Sun X , Lin Y , Zou X , Li Z , Liao Y , et al . Endothelial cell injury and dysfunction induced by silver nanoparticles through oxidative stress via IKK/NF-kappaB pathways . Biomaterials . 2014 ; 35 : 6657 - 66 .
Kucharczak J , Simmons MJ , Fan Y , Gelinas C . To be, or not to be: NF-kappaB is the answer–role of Rel/NF-kappaB in the regulation of apoptosis . Oncogene . 2003 ; 22 : 8961 - 82 .
Zhong CY , Zhou YM , Pinkerton KE . NF-kappaB inhibition is involved in tobacco smoke-induced apoptosis in the lungs of rats . Toxicol Appl Pharmacol . 2008 ; 230 : 150 - 8 .
Balogova L , Maslanakova M , Dzurova L , Miskovsky P , Stroffekova K . Bcl-2 proapoptotic proteins distribution in U-87 MG glioma cells before and after hypericin photodynamic action . Gen Physiol Biophys . 2013 ; 32 : 179 - 87 .
Hu B , Sun M , Liu J , Hong G , Lin Q . The preventative effect of Akt knockout on liver cancer through modulating NF-κB-regulated inflammation and badrelated apoptosis signaling pathway . Int J Oncol . 2016 ; 48 : 1467 .
Riedl SJ , Shi Y . Molecular mechanisms of caspase regulation during apoptosis . Nat Rev Mol Cell Biol . 2004 ; 5 : 897 - 907 .
Twomey C , McCarthy JV . Pathways of apoptosis and importance in development . J Cell Mol Med . 2005 ; 9 : 345 - 59 .
Deng F , Guo X , Liu H , Fang X , Yang M , Chen W . Effects of dust storm PM2.5 on cell proliferation and cell cycle in human lung fibroblasts . Toxicol In Vitro . 2007 ; 21 : 632 - 8 .
Tang CH , Yang RS , Fu WM . Prostaglandin E2 stimulates fibronectin expression through EP1 receptor, phospholipase C, protein kinase Calpha, and c-Src pathway in primary cultured rat osteoblasts . J Biol Chem . 2005 ; 280 : 22907 - 16 .
Woods CG , Fu J , Xue P , Hou Y , Pluta LJ , Yang L , et al . Dose-dependent transitions in Nrf2-mediated adaptive response and related stress responses to hypochlorous acid in mouse macrophages . Toxicol Appl Pharmacol . 2009 ; 238 : 27 - 36 .
Maier KL , Alessandrini F , Beck-Speier I , Hofer TP , Diabate S , Bitterle E , et al . Health effects of ambient particulate matter–biological mechanisms and inflammatory responses to in vitro and in vivo particle exposures . Inhal Toxicol . 2008 ; 20 : 319 - 37 .
Kaplan GG , Dixon E , Panaccione R , Fong A , Chen L , Szyszkowicz M , et al . Effect of ambient air pollution on the incidence of appendicitis . CMAJ . 2009 ; 181 : 591 - 7 .
Orazzo F , Nespoli L , Ito K , Tassinari D , Giardina D , Funis M , et al . Air pollution, aeroallergens, and emergency room visits for acute respiratory diseases and gastroenteric disorders among young children in six Italian cities . Environ Health Perspect . 2009 ; 117 : 1780 - 5 .
Kim HR , Lee JE , Jeong MH , Choi SJ , Lee K , Chung KH . Comparative evaluation of the mutagenicity and genotoxicity of smoke condensate derived from Korean cigarettes . Environ Health Toxicol . 2015 ; 30 : e2015014 .
Li X , Peng B , Nie C , Shang P , Liu H . Evaluation of the cytotoxicity of cigarette smoke total particulate matter using three in vitro assays and two types of cells . Toxicol Mech Methods . 2013 ; 23 : 240 - 6 .
Lin B , Li X , Zhang H , Lin Z , Tian L , Nie C , et al . Comparison of in vitro toxicity of mainstream cigarette smoke particulate matter from nano- to micro-size . Food Chem Toxicol . 2014 ; 64 : 353 - 60 .
Nara H , Fukano Y , Nishino T , Aufderheide M . Detection of the cytotoxicity of water-insoluble fraction of cigarette smoke by direct exposure to cultured cells at an air-liquid interface . Exp Toxicol Pathol . 2013 ; 65 : 683 - 8 .
Chen H , Cui L , Jiang XY , Pang YQ , Tang GL , Hou HW , et al . Evaluation of the cytotoxicity of cigarette smoke condensate by a cellular impedance biosensor . Food Chem Toxicol . 2012 ; 50 : 612 - 8 .
Lodovici M , Bigagli E . Oxidative stress and air pollution exposure . J Toxicol . 2011 ; 2011 : 487074 .
Manna SK , Mukhopadhyay A , Aggarwal BB . IFN-alpha suppresses activation of nuclear transcription factors NF-kappa B and activator protein 1 and potentiates TNF-induced apoptosis . J Immunol . 2000 ; 165 : 4927 - 34 .
Takada Y , Aggarwal BB . Betulinic acid suppresses carcinogen-induced NFkappa B activation through inhibition of I kappa B alpha kinase and p65 phosphorylation: abrogation of cyclooxygenase-2 and matrix metalloprotease-9 . J Immunol . 2003 ; 171 : 3278 - 86 .
Huang YC , Hsiao YC , Chen YJ , Wei YY , Lai TH , Tang CH . Stromal cell-derived factor-1 enhances motility and integrin up-regulation through CXCR4, ERK and NF-kappaB-dependent pathway in human lung cancer cells . Biochem Pharmacol . 2007 ; 74 : 1702 - 12 .
Hasnis E , Bar-Shai M , Burbea Z , Reznick AZ . Mechanisms underlying cigarette smoke-induced NF-kappaB activation in human lymphocytes: the role of reactive nitrogen species . J Physiol Pharmacol . 2007 ; 58 ( Suppl 5 ): 275 - 87 .
Nam HY , Choi BH , Lee JY , Lee SG , Kim YH , Lee KH , et al . The role of nitric oxide in the particulate matter (PM 2.5 )-induced NFkappaB activation in lung epithelial cells . Toxicol Lett . 2004 ; 148 : 95 - 102 .
Dagher Z , Garcon G , Billet S , Gosset P , Ledoux F , Courcot D , et al . Activation of different pathways of apoptosis by air pollution particulate matter (PM2.5) in human epithelial lung cells (L132) in culture . Toxicology . 2006 ; 225 : 12 - 24 .
Shishodia S , Aggarwal BB . Cyclooxygenase (COX)-2 inhibitor celecoxib abrogates activation of cigarette smoke-induced nuclear factor (NF)-kappaB by suppressing activation of IkappaBalpha kinase in human non-small cell lung carcinoma: correlation with suppression of cyclin D1, COX-2, and matrix metalloproteinase-9 . Cancer Res . 2004 ; 64 : 5004 - 12 .
Roy SS , Madesh M , Davies E , Antonsson B , Danial N , Hajnóczky G . Bad targets the permeability transition pore independent of Bax or Bak to switch between Ca 2+ -dependent cell survival and death . Mol Cell . 2009 ; 33 : 377 - 88 .
Ash C , Cruz M . Self-protection mechanism . Science . 2010 ; 330 : 1153 .
Sowmya SG , Yogendra PK , Arpitha HS , Deepika UR , Nawneet KK , Mondal P , et al . β-carotene at physiologically attainable concentration induces apoptosis and down-regulates cell survival and antioxidant markers in human breast cancer (MCF-7) cells . Mol Cell Biochem . 2017 . doi: 10.1007/s11010-017-3071-4 10.1007/s11010-017-3071-4 . [Epub ahead of print] .
Chang F , Lee JT , Navolanic PM , Steelman LS , Shelton JG , Blalock WL , et al . Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy . Leukemia . 2003 ; 17 : 590 - 603 .
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