HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 27/4/705    most recent 09031936.06.00012805v1 Alert me when this article is cited Alert me if a correction is posted Permissions Request Permissions Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Bayram, H. Articles by Chung, K. F. Search for Related Content PubMed PubMed Citation Articles by Bayram, H. Articles by Chung, K. F.

Regulation of human lung epithelial cell numbers by diesel exhaust particles

¹ Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, UK. ² Dept of Respiratory Medicine, School of Medicine, Dicle University, Diyarbakir, Turkey.

CORRESPONDENCE: K. F. Chung, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK. Fax: 44 2073518126. E-mail: f.chung{at}imperial.ac.uk

Keywords: Antioxidants, apoptosis, cell proliferation, diesel exhaust particles, nuclear factor-B

Received: February 5, 2005
Accepted January 4, 2006

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 µg·mL^–1) prevented this. Using flow cytometric analysis of propidium iodide (PI) staining, DEP (10 µg·mL^–1) increased cells in the S phase of cell cycle from 12.85 to 18.75% after 48 h, reversing serum starvation-induced G_0/1 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 µM), the N-terminal c-jun kinase inhibitor, SP600125 (33 µM), and nuclear factor-B inhibitor, SN50 (33 µM), inhibited DEP-induced cell number increase. NAC inhibited DEP-induced reduction of G_0/1 and increase in cells in the S and G₂/M phases. Expression of p21^CIP1/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 p21^CIP1/WAF1 expression and stimulation of N-terminal c-jun kinase and nuclear factor-B. Therefore, low-dose diesel exhaust particle exposure may lead to lung epithelial cell hyperplasia.

This article has been cited by other articles:

				L. Muller, M. Riediker, P. Wick, M. Mohr, P. Gehr, and B. Rothen-Rutishauser Oxidative stress and inflammation response after nanoparticle exposure: differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways J R Soc Interface, February 6, 2010; 7(Suppl_1): S27 - S40. [Abstract] [Full Text] [PDF]

				D. Cao, P. A. Bromberg, and J. M. Samet Diesel Particle-Induced Transcriptional Expression of p21 Involves Activation of EGFR, Src, and Stat3 Am. J. Respir. Cell Mol. Biol., January 1, 2010; 42(1): 88 - 95. [Abstract] [Full Text] [PDF]

				T. Stevens, Q. T. Krantz, W. P. Linak, S. Hester, and M. I. Gilmour Increased Transcription of Immune and Metabolic Pathways in Naive and Allergic Mice Exposed to Diesel Exhaust Toxicol. Sci., April 1, 2008; 102(2): 359 - 370. [Abstract] [Full Text] [PDF]

				M. Martinez-Losa, J. Cortijo, G. Juan, M. Ramon, M. J. Sanz, and E. J. Morcillo Modulatory effects of N-acetyl-L-cysteine on human eosinophil apoptosis Eur. Respir. J., September 1, 2007; 30(3): 436 - 442. [Abstract] [Full Text] [PDF]

				N. Li and A. E. Nel The cellular impacts of diesel exhaust particles: beyond inflammation and death. Eur. Respir. J., April 1, 2006; 27(4): 667 - 668. [Full Text] [PDF]