Regulation of human lung epithelial cell numbers by diesel exhaust particles.
Particulate air pollution is associated with respiratory morbidity and has cytotoxic and pro-inflammatory effects. The effects of diesel exhaust particles (DEP) on proliferation and apoptosis of A549 lung epithelial cells were examined. When deprived of serum (serum starvation), epithelial cell numbers fell, but DEP (5-200 microg.mL-1) prevented this. Using flow cytometric analysis of propidium iodide (PI) staining, DEP (10 microg.mL-1) increased cells in the S phase of cell cycle from 12.85 to 18.75% after 48 h, reversing serum starvation-induced G0/1 arrest. DEP also reduced the increase in apoptotic cells, as defined by double expression of annexin V/PI, observed after serum starvation (from 28.35 to 15.46%). The antioxidants, N-acetylcysteine (NAC; 33 mM) and AEOL10113 (10-100 microM), the N-terminal c-jun kinase inhibitor, SP600125 (33 microM), and nuclear factor-kappaB inhibitor, SN50 (33 microM), inhibited DEP-induced cell number increase. NAC inhibited DEP-induced reduction of G0/1 and increase in cells in the S and G2/M phases. Expression of p21CIP1/WAF1 mRNA and protein seen with serum starvation was reduced by DEP. In conclusion, diesel exhaust particles prevented serum starvation-led decreases in A549 epithelial cells by inducing cell cycle progression and preventing apoptosis, processes involving oxidative stress, inhibition of p21CIP1/WAF1 expression and stimulation of N-terminal c-jun kinase and nuclear factor-kappaB. Therefore, low-dose diesel exhaust particle exposure may lead to lung epithelial cell hyperplasia.
Bayram
H
H
Thoracic Medicine, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
Ito
K
K
Issa
R
R
Ito
M
M
Sukkar
M
M
Chung
K F
KF
D017209:Apoptosis / Q000502:physiology*; D002452:Cell Count; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004847:Epithelial Cells / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D016328:NF-kappa B / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D010316:Particle Size; D011014:Pneumonia / Q000503:physiopathology*; D012333:RNA, Messenger / Q000235:genetics; D020545:Respiratory Mucosa / Q000502:physiology*; D001335:Vehicle Emissions / Q000633:toxicity*
C493956:CDKN1A protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016328:NF-kappa B; D012333:RNA, Messenger; D001335:Vehicle Emissions; D051357:Cyclin-Dependent Kinase 2