This Article Full Text Full Text (PDF) All Versions of this Article: 2002-0321OCv1 29/3/331    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal 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 Google Scholar Google Scholar Articles by Hackett, N. R. Articles by Crystal, R. G. Search for Related Content PubMed PubMed Citation Articles by Hackett, N. R. Articles by Crystal, R. G.

Variability of Antioxidant-Related Gene Expression in the Airway Epithelium of Cigarette Smokers

Belfer Gene Therapy Core Facility, Department of Genetic Medicine, Division of Pulmonary and Critical Care Medicine, and Department of Pathology, Weill Medical College of Cornell University, New York, New York

Address correspondence to: Ronald G. Crystal, Department of Genetic Medicine, Weill Medical College of Cornell University, 515 East 71st Street, Suite 1000, New York, New York 10021. E-mail: geneticmedicine{at}med.cornell.edu

Cigarette smoking is the major risk factor for developing chronic bronchitis, yet only 15–20% of smokers develop this disorder. Because oxidants are the major mechanism of smoking-induced airway damage, we hypothesized that smoking is associated with upregulation of various antioxidant-related genes in the airway epithelium, but the magnitude of the response shows high inter-individual variability. Microarray analysis was used to assess levels of expression of 44 antioxidant-related genes in four categories (catalase/superoxide dismutase family; glutathione metabolism; redox balance; and pentose phosphate cycle) in bronchoscopy-obtained airway epithelium of matched cohorts (13 current smokers, 9 nonsmokers), none of whom had lung disease. There was minimal variation in gene expression levels within the same individual (right versus left lung or over time), but significant upregulation of 16/44 antioxidant-related genes in smoker epithelium compared with nonsmokers. Subgroups of smokers were identified with clusters of expression levels of antioxidant-related genes. We propose that the antioxidant-related genes demonstrating the most variability in the level of expression in smokers may be useful genetic markers in epidemiologic studies assessing susceptibility to smoking-induced chronic bronchitis.

Abbreviations: 1-antitrypsin, AAT • chronic obstructive pulmonary disease, COPD • coefficient of variation, CV • epithelial lining fluid, ELF • -glutamate cysteine ligase, GCL • superoxide dismutase, SOD

This article has been cited by other articles:

				J. E. Zeskind, M. E. Lenburg, and A. Spira Translating the COPD Transcriptome: Insights into Pathogenesis and Tools for Clinical Management Proceedings of the ATS, December 1, 2008; 5(8): 834 - 841. [Abstract] [Full Text] [PDF]

				K. Steiling, J. Ryan, J. S. Brody, and A. Spira The Field of Tissue Injury in the Lung and Airway Cancer Prevention Research, November 1, 2008; 1(6): 396 - 403. [Abstract] [Full Text] [PDF]

				A R Bentley, P Emrani, and P A Cassano Genetic variation and gene expression in antioxidant related enzymes and risk of COPD: a systematic review Thorax, November 1, 2008; 63(11): 956 - 961. [Abstract] [Full Text] [PDF]

				B. J. Carolan, B.-G. Harvey, B. P. De, H. Vanni, and R. G. Crystal Decreased Expression of Intelectin 1 in the Human Airway Epithelium of Smokers Compared to Nonsmokers J. Immunol., October 15, 2008; 181(8): 5760 - 5767. [Abstract] [Full Text] [PDF]

				T. L. Adair-Kirk, J. J. Atkinson, G. L. Griffin, M. A. Watson, D. G. Kelley, D. DeMello, R. M. Senior, and T. Betsuyaku Distal Airways in Mice Exposed to Cigarette Smoke: Nrf2-Regulated Genes Are Increased in Clara Cells Am. J. Respir. Cell Mol. Biol., October 1, 2008; 39(4): 400 - 411. [Abstract] [Full Text] [PDF]

				R. G. Crystal, S. H. Randell, J. F. Engelhardt, J. Voynow, and M. E. Sunday Airway Epithelial Cells: Current Concepts and Challenges Proceedings of the ATS, September 15, 2008; 5(7): 772 - 777. [Abstract] [Full Text] [PDF]

				K. Pawlowski Uncharacterized/hypothetical proteins in biomedical 'omics' experiments: is novelty being swept under the carpet? Brief Funct Genomic Proteomic, July 19, 2008; (2008) eln033v1. [Abstract] [Full Text] [PDF]

				M. Siedlinski, D. S. Postma, C. C. van Diemen, A. Blokstra, H. A. Smit, and H. M. Boezen Lung Function Loss, Smoking, Vitamin C Intake, and Polymorphisms of the Glutamate-Cysteine Ligase Genes Am. J. Respir. Crit. Care Med., July 1, 2008; 178(1): 13 - 19. [Abstract] [Full Text] [PDF]

				K. F. Chung and I. M. Adcock Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction Eur. Respir. J., June 1, 2008; 31(6): 1334 - 1356. [Abstract] [Full Text] [PDF]

				Z. Ammous, N. R. Hackett, M. W. Butler, T. Raman, I. Dolgalev, T. P. O'Connor, B.-G. Harvey, and R. G. Crystal Variability in Small Airway Epithelial Gene Expression Among Normal Smokers Chest, June 1, 2008; 133(6): 1344 - 1353. [Abstract] [Full Text] [PDF]

				S. G. Kelsen, X. Duan, R. Ji, O. Perez, C. Liu, and S. Merali Cigarette Smoke Induces an Unfolded Protein Response in the Human Lung: A Proteomic Approach Am. J. Respir. Cell Mol. Biol., May 1, 2008; 38(5): 541 - 550. [Abstract] [Full Text] [PDF]

				D. Ucar, I. Neuhaus, P. Ross-MacDonald, C. Tilford, S. Parthasarathy, N. Siemers, and R.-R. Ji Construction of a reference gene association network from multiple profiling data: application to data analysis Bioinformatics, October 15, 2007; 23(20): 2716 - 2724. [Abstract] [Full Text] [PDF]

				F. Kassie, L. B. Anderson, R. Scherber, N. Yu, D. Lahti, P. Upadhyaya, and S. S. Hecht Indole-3-carbinol Inhibits 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone Plus Benzo(a)pyrene-Induced Lung Tumorigenesis in A/J Mice and Modulates Carcinogen-Induced Alterations in Protein Levels Cancer Res., July 1, 2007; 67(13): 6502 - 6511. [Abstract] [Full Text] [PDF]

				T. Yoshida and R. M. Tuder Pathobiology of Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease Physiol Rev, July 1, 2007; 87(3): 1047 - 1082. [Abstract] [Full Text] [PDF]

				H. Maunders, S. Patwardhan, J. Phillips, A. Clack, and A. Richter Human bronchial epithelial cell transcriptome: gene expression changes following acute exposure to whole cigarette smoke in vitro Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1248 - L1256. [Abstract] [Full Text] [PDF]

				A. Heguy, B.-G. Harvey, P. L. Leopold, I. Dolgalev, T. Raman, and R. G. Crystal Responses of the human airway epithelium transcriptome to in vivo injury Physiol Genomics, April 24, 2007; 29(2): 139 - 148. [Abstract] [Full Text] [PDF]

				S. Pierrou, P. Broberg, R. A. O'Donnell, K. Pawlowski, R. Virtala, E. Lindqvist, A. Richter, S. J. Wilson, G. Angco, S. Moller, et al. Expression of Genes Involved in Oxidative Stress Responses in Airway Epithelial Cells of Smokers with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., March 15, 2007; 175(6): 577 - 586. [Abstract] [Full Text] [PDF]

				A. C. Borczuk and C. A. Powell Expression Profiling and Lung Cancer Development Proceedings of the ATS, January 1, 2007; 4(1): 127 - 132. [Abstract] [Full Text] [PDF]

				A. Singh, T. Rangasamy, R. K. Thimmulappa, H. Lee, W. O. Osburn, R. Brigelius-Flohe, T. W. Kensler, M. Yamamoto, and S. Biswal Glutathione Peroxidase 2, the Major Cigarette Smoke-Inducible Isoform of GPX in Lungs, Is Regulated by Nrf2 Am. J. Respir. Cell Mol. Biol., December 1, 2006; 35(6): 639 - 650. [Abstract] [Full Text] [PDF]

				K. M. Lonergan, R. Chari, R. J. deLeeuw, A. Shadeo, B. Chi, M.-S. Tsao, S. Jones, M. Marra, V. Ling, R. Ng, et al. Identification of Novel Lung Genes in Bronchial Epithelium by Serial Analysis of Gene Expression Am. J. Respir. Cell Mol. Biol., December 1, 2006; 35(6): 651 - 661. [Abstract] [Full Text] [PDF]

				B. J. Carolan, A. Heguy, B.-G. Harvey, P. L. Leopold, B. Ferris, and R. G. Crystal Up-regulation of Expression of the Ubiquitin Carboxyl-Terminal Hydrolase L1 Gene in Human Airway Epithelium of Cigarette Smokers. Cancer Res., November 15, 2006; 66(22): 10729 - 10740. [Abstract] [Full Text] [PDF]

				A. Chambellan, P. J. Cruickshank, P. McKenzie, S. B. Cannady, K. Szabo, S. A. A. Comhair, and S. C. Erzurum Gene Expression Profile of Human Airway Epithelium Induced by Hyperoxia In Vivo Am. J. Respir. Cell Mol. Biol., October 1, 2006; 35(4): 424 - 435. [Abstract] [Full Text] [PDF]

				M. P. Gruber, C. D. Coldren, M. D. Woolum, G. P. Cosgrove, C. Zeng, A. E. Baron, M. D. Moore, C. D. Cool, G. S. Worthen, K. K. Brown, et al. Human Lung Project: Evaluating Variance of Gene Expression in the Human Lung Am. J. Respir. Cell Mol. Biol., July 1, 2006; 35(1): 65 - 71. [Abstract] [Full Text] [PDF]

				V L Kinnula Focus on antioxidant enzymes and antioxidant strategies in smoking related airway diseases Thorax, August 1, 2005; 60(8): 693 - 700. [Abstract] [Full Text] [PDF]

				W. R. Fields, R. M. Leonard, P. S. Odom, B. K. Nordskog, M. W. Ogden, and D. J. Doolittle Gene Expression in Normal Human Bronchial Epithelial (NHBE) Cells Following In Vitro Exposure to Cigarette Smoke Condensate Toxicol. Sci., July 1, 2005; 86(1): 84 - 91. [Abstract] [Full Text] [PDF]

				P. J. Barnes and R. A. Stockley COPD: current therapeutic interventions and future approaches Eur. Respir. J., June 1, 2005; 25(6): 1084 - 1106. [Abstract] [Full Text] [PDF]

				T. Harju, R. Kaarteenaho-Wiik, R. Sirvio, P. Paakko, J.D. Crapo, T.D. Oury, Y. Soini, and V.L. Kinnula Manganese superoxide dismutase is increased in the airways of smokers' lungs Eur. Respir. J., November 1, 2004; 24(5): 765 - 771. [Abstract] [Full Text] [PDF]

				S. Fuke, T. Betsuyaku, Y. Nasuhara, T. Morikawa, H. Katoh, and M. Nishimura Chemokines in Bronchiolar Epithelium in the Development of Chronic Obstructive Pulmonary Disease Am. J. Respir. Cell Mol. Biol., October 1, 2004; 31(4): 405 - 412. [Abstract] [Full Text] [PDF]

				A. Spira, J. Beane, V. Shah, G. Liu, F. Schembri, X. Yang, J. Palma, and J. S. Brody Effects of cigarette smoke on the human airway epithelial cell transcriptome PNAS, July 6, 2004; 101(27): 10143 - 10148. [Abstract] [Full Text] [PDF]