The University of Southampton
University of Southampton Institutional Repository

Expression of genes involved in oxidative stress responses in airway epithelial cells of smokers with chronic obstructive pulmonary disease

Expression of genes involved in oxidative stress responses in airway epithelial cells of smokers with chronic obstructive pulmonary disease
Expression of genes involved in oxidative stress responses in airway epithelial cells of smokers with chronic obstructive pulmonary disease
RATIONALE: The molecular mechanisms involved in airway oxidative stress responses reported in healthy smokers and in those with chronic obstructive pulmonary disease (COPD) are poorly understood.

OBJECTIVES: To assess the expression of genes involved in oxidative stress responses in the bronchial epithelium of smokers with or without COPD and in relation to disease severity.

METHODS: Global gene expression was assessed in bronchial brushings in 38 subjects with COPD, 14 healthy nonsmokers, and 18 healthy smokers.

RESULTS: Gene expression analysis using Affymetrix arrays revealed mRNAs representing 341 out of 642 oxidative stress genes from two predefined gene sets to be differentially expressed in healthy nonsmokers when compared with healthy smokers, and 200 differentially expressed oxidative genes in subjects with COPD when compared with healthy smokers. Gene set enrichment analysis showed that pathways involved in oxidant/antioxidant responses were among the most differentially expressed gene pathways in smoking individuals, with further differences seen in COPD. Distinct, nonlinear gene expression patterns were identified across the severity spectrum of COPD, which correlated with the presence of certain transcription factor binding sites in their promoters. Significant changes in oxidant response genes observed in vivo were reproduced in vitro using primary bronchial epithelial cells from the same donors cultured at an air-liquid interface and exposed to cigarette smoke extract. CONCLUSIONS: Cigarette smoke induces significant changes in oxidant defense responses; some of these are further amplified, but not in a linear fashion, in individuals who develop COPD.
pulmonary disease, chronic obstructive, oligonucleotidearray sequence analysis
1073-449X
577-586
Pierrou, Stefan
e4ad6051-90a5-4378-bad8-c8837dcc456d
Broberg, Per
c2c0de25-1441-473b-b57e-7c8784513dc6
O’Donnell, Rory A.
fd6279bc-ddab-4ea7-b171-19a3661e4874
Pawłowski, Krzysztof
6b064e63-a169-47c1-8400-b091af128c51
Virtala, Robert
eb1569c7-cde2-40d5-a42b-2ac59b6c52d2
Lindqvist, Eva
29aeb1d6-8e86-40af-b66a-b2f56a497eea
Richter, Audrey
5b4fb888-b3a7-4b81-a8a7-ffd2c046a196
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Angco, Gilbert
8f4d5efe-fa0c-4953-b255-3d221bcd16ab
Möller, Sebastian
58e09438-0c2a-4f9b-9027-754b725f2833
Bergstrand, Håkan
48e46cff-3c2b-4561-964f-dff893bdf664
Koopmann, Witte
4bd4c7d2-e045-4398-b8c1-2b3c63ad32f7
Wieslander, Elisabet
1d7c92c5-cbdd-4231-b6c2-dd390ff44738
Strömstedt, Per-Erik
4da02806-7e1b-4baa-b477-3ace629c4f53
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Lund, Johan
28594211-985f-41cc-94af-229ec7400bbb
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Pierrou, Stefan
e4ad6051-90a5-4378-bad8-c8837dcc456d
Broberg, Per
c2c0de25-1441-473b-b57e-7c8784513dc6
O’Donnell, Rory A.
fd6279bc-ddab-4ea7-b171-19a3661e4874
Pawłowski, Krzysztof
6b064e63-a169-47c1-8400-b091af128c51
Virtala, Robert
eb1569c7-cde2-40d5-a42b-2ac59b6c52d2
Lindqvist, Eva
29aeb1d6-8e86-40af-b66a-b2f56a497eea
Richter, Audrey
5b4fb888-b3a7-4b81-a8a7-ffd2c046a196
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Angco, Gilbert
8f4d5efe-fa0c-4953-b255-3d221bcd16ab
Möller, Sebastian
58e09438-0c2a-4f9b-9027-754b725f2833
Bergstrand, Håkan
48e46cff-3c2b-4561-964f-dff893bdf664
Koopmann, Witte
4bd4c7d2-e045-4398-b8c1-2b3c63ad32f7
Wieslander, Elisabet
1d7c92c5-cbdd-4231-b6c2-dd390ff44738
Strömstedt, Per-Erik
4da02806-7e1b-4baa-b477-3ace629c4f53
Holgate, Stephen T.
2e7c17a9-6796-436e-8772-1fe6d2ac5edc
Davies, Donna E.
7de8fdc7-3640-4e3a-aa91-d0e03f990c38
Lund, Johan
28594211-985f-41cc-94af-229ec7400bbb
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d

Pierrou, Stefan, Broberg, Per, O’Donnell, Rory A., Pawłowski, Krzysztof, Virtala, Robert, Lindqvist, Eva, Richter, Audrey, Wilson, Susan J., Angco, Gilbert, Möller, Sebastian, Bergstrand, Håkan, Koopmann, Witte, Wieslander, Elisabet, Strömstedt, Per-Erik, Holgate, Stephen T., Davies, Donna E., Lund, Johan and Djukanovic, Ratko (2007) Expression of genes involved in oxidative stress responses in airway epithelial cells of smokers with chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine, 175 (6), 577-586. (doi:10.1164/rccm.200607-931OC).

Record type: Article

Abstract

RATIONALE: The molecular mechanisms involved in airway oxidative stress responses reported in healthy smokers and in those with chronic obstructive pulmonary disease (COPD) are poorly understood.

OBJECTIVES: To assess the expression of genes involved in oxidative stress responses in the bronchial epithelium of smokers with or without COPD and in relation to disease severity.

METHODS: Global gene expression was assessed in bronchial brushings in 38 subjects with COPD, 14 healthy nonsmokers, and 18 healthy smokers.

RESULTS: Gene expression analysis using Affymetrix arrays revealed mRNAs representing 341 out of 642 oxidative stress genes from two predefined gene sets to be differentially expressed in healthy nonsmokers when compared with healthy smokers, and 200 differentially expressed oxidative genes in subjects with COPD when compared with healthy smokers. Gene set enrichment analysis showed that pathways involved in oxidant/antioxidant responses were among the most differentially expressed gene pathways in smoking individuals, with further differences seen in COPD. Distinct, nonlinear gene expression patterns were identified across the severity spectrum of COPD, which correlated with the presence of certain transcription factor binding sites in their promoters. Significant changes in oxidant response genes observed in vivo were reproduced in vitro using primary bronchial epithelial cells from the same donors cultured at an air-liquid interface and exposed to cigarette smoke extract. CONCLUSIONS: Cigarette smoke induces significant changes in oxidant defense responses; some of these are further amplified, but not in a linear fashion, in individuals who develop COPD.

Full text not available from this repository.

More information

Published date: 2007
Keywords: pulmonary disease, chronic obstructive, oligonucleotidearray sequence analysis

Identifiers

Local EPrints ID: 146537
URI: https://eprints.soton.ac.uk/id/eprint/146537
ISSN: 1073-449X
PURE UUID: e0e10ee0-5702-4a33-b1d4-12ccfe8dd91c
ORCID for Donna E. Davies: ORCID iD orcid.org/0000-0002-5117-2991
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

Catalogue record

Date deposited: 03 Jun 2010 09:18
Last modified: 07 Aug 2019 00:54

Export record

Altmetrics

Contributors

Author: Stefan Pierrou
Author: Per Broberg
Author: Rory A. O’Donnell
Author: Krzysztof Pawłowski
Author: Robert Virtala
Author: Eva Lindqvist
Author: Audrey Richter
Author: Susan J. Wilson
Author: Gilbert Angco
Author: Sebastian Möller
Author: Håkan Bergstrand
Author: Witte Koopmann
Author: Elisabet Wieslander
Author: Per-Erik Strömstedt
Author: Donna E. Davies ORCID iD
Author: Johan Lund

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×