Disparate oxidant gene expression of airway epithelium compared to alveolar macrophages in smokers

Brendan J. Carolan, Ben Gary Harvey, Neil R. Hackett, Timothy P. O'Connor, Patricia A. Cassano, Ronald Crystal

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background: The small airway epithelium and alveolar macrophages are exposed to oxidants in cigarette smoke leading to epithelial dysfunction and macrophage activation. In this context, we asked: what is the transcriptome of oxidant-related genes in small airway epithelium and alveolar macrophages, and does their response differ substantially to inhaled cigarette smoke?Methods: Using microarray analysis, with TaqMan RT-PCR confirmation, we assessed oxidant-related gene expression in small airway epithelium and alveolar macrophages from the same healthy nonsmoker and smoker individuals.Results: Of 155 genes surveyed, 87 (56%) were expressed in both cell populations in nonsmokers, with higher expression in alveolar macrophages (43%) compared to airway epithelium (24%). In smokers, there were 15 genes (10%) up-regulated and 7 genes (5%) down-regulated in airway epithelium, but only 3 (2%) up-regulated and 2 (1%) down-regulated in alveolar macrophages. Pathway analysis of airway epithelium showed oxidant pathways dominated, but in alveolar macrophages immune pathways dominated.Conclusion: Thus, the response of different cell-types with an identical genome exposed to the same stress of smoking is different; responses of alveolar macrophages are more subdued than those of airway epithelium. These findings are consistent with the observation that, while the small airway epithelium is vulnerable, alveolar macrophages are not "diseased" in response to smoking.Trial Registration: ClinicalTrials.gov ID: NCT00224185 and NCT00224198.

Original languageEnglish
Article number111
JournalRespiratory Research
Volume10
DOIs
Publication statusPublished - 17 Nov 2009
Externally publishedYes

Fingerprint

Alveolar Macrophages
Oxidants
Epithelium
Gene Expression
Smoke
Tobacco Products
Genes
Smoking
Macrophage Activation
Microarray Analysis
Transcriptome
Genome
Polymerase Chain Reaction
Population

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Disparate oxidant gene expression of airway epithelium compared to alveolar macrophages in smokers. / Carolan, Brendan J.; Harvey, Ben Gary; Hackett, Neil R.; O'Connor, Timothy P.; Cassano, Patricia A.; Crystal, Ronald.

In: Respiratory Research, Vol. 10, 111, 17.11.2009.

Research output: Contribution to journalArticle

Carolan, Brendan J. ; Harvey, Ben Gary ; Hackett, Neil R. ; O'Connor, Timothy P. ; Cassano, Patricia A. ; Crystal, Ronald. / Disparate oxidant gene expression of airway epithelium compared to alveolar macrophages in smokers. In: Respiratory Research. 2009 ; Vol. 10.
@article{0f23d72c27f8485da2af6b75e7ce4d21,
title = "Disparate oxidant gene expression of airway epithelium compared to alveolar macrophages in smokers",
abstract = "Background: The small airway epithelium and alveolar macrophages are exposed to oxidants in cigarette smoke leading to epithelial dysfunction and macrophage activation. In this context, we asked: what is the transcriptome of oxidant-related genes in small airway epithelium and alveolar macrophages, and does their response differ substantially to inhaled cigarette smoke?Methods: Using microarray analysis, with TaqMan RT-PCR confirmation, we assessed oxidant-related gene expression in small airway epithelium and alveolar macrophages from the same healthy nonsmoker and smoker individuals.Results: Of 155 genes surveyed, 87 (56{\%}) were expressed in both cell populations in nonsmokers, with higher expression in alveolar macrophages (43{\%}) compared to airway epithelium (24{\%}). In smokers, there were 15 genes (10{\%}) up-regulated and 7 genes (5{\%}) down-regulated in airway epithelium, but only 3 (2{\%}) up-regulated and 2 (1{\%}) down-regulated in alveolar macrophages. Pathway analysis of airway epithelium showed oxidant pathways dominated, but in alveolar macrophages immune pathways dominated.Conclusion: Thus, the response of different cell-types with an identical genome exposed to the same stress of smoking is different; responses of alveolar macrophages are more subdued than those of airway epithelium. These findings are consistent with the observation that, while the small airway epithelium is vulnerable, alveolar macrophages are not {"}diseased{"} in response to smoking.Trial Registration: ClinicalTrials.gov ID: NCT00224185 and NCT00224198.",
author = "Carolan, {Brendan J.} and Harvey, {Ben Gary} and Hackett, {Neil R.} and O'Connor, {Timothy P.} and Cassano, {Patricia A.} and Ronald Crystal",
year = "2009",
month = "11",
day = "17",
doi = "10.1186/1465-9921-10-111",
language = "English",
volume = "10",
journal = "Respiratory Research",
issn = "1465-9921",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Disparate oxidant gene expression of airway epithelium compared to alveolar macrophages in smokers

AU - Carolan, Brendan J.

AU - Harvey, Ben Gary

AU - Hackett, Neil R.

AU - O'Connor, Timothy P.

AU - Cassano, Patricia A.

AU - Crystal, Ronald

PY - 2009/11/17

Y1 - 2009/11/17

N2 - Background: The small airway epithelium and alveolar macrophages are exposed to oxidants in cigarette smoke leading to epithelial dysfunction and macrophage activation. In this context, we asked: what is the transcriptome of oxidant-related genes in small airway epithelium and alveolar macrophages, and does their response differ substantially to inhaled cigarette smoke?Methods: Using microarray analysis, with TaqMan RT-PCR confirmation, we assessed oxidant-related gene expression in small airway epithelium and alveolar macrophages from the same healthy nonsmoker and smoker individuals.Results: Of 155 genes surveyed, 87 (56%) were expressed in both cell populations in nonsmokers, with higher expression in alveolar macrophages (43%) compared to airway epithelium (24%). In smokers, there were 15 genes (10%) up-regulated and 7 genes (5%) down-regulated in airway epithelium, but only 3 (2%) up-regulated and 2 (1%) down-regulated in alveolar macrophages. Pathway analysis of airway epithelium showed oxidant pathways dominated, but in alveolar macrophages immune pathways dominated.Conclusion: Thus, the response of different cell-types with an identical genome exposed to the same stress of smoking is different; responses of alveolar macrophages are more subdued than those of airway epithelium. These findings are consistent with the observation that, while the small airway epithelium is vulnerable, alveolar macrophages are not "diseased" in response to smoking.Trial Registration: ClinicalTrials.gov ID: NCT00224185 and NCT00224198.

AB - Background: The small airway epithelium and alveolar macrophages are exposed to oxidants in cigarette smoke leading to epithelial dysfunction and macrophage activation. In this context, we asked: what is the transcriptome of oxidant-related genes in small airway epithelium and alveolar macrophages, and does their response differ substantially to inhaled cigarette smoke?Methods: Using microarray analysis, with TaqMan RT-PCR confirmation, we assessed oxidant-related gene expression in small airway epithelium and alveolar macrophages from the same healthy nonsmoker and smoker individuals.Results: Of 155 genes surveyed, 87 (56%) were expressed in both cell populations in nonsmokers, with higher expression in alveolar macrophages (43%) compared to airway epithelium (24%). In smokers, there were 15 genes (10%) up-regulated and 7 genes (5%) down-regulated in airway epithelium, but only 3 (2%) up-regulated and 2 (1%) down-regulated in alveolar macrophages. Pathway analysis of airway epithelium showed oxidant pathways dominated, but in alveolar macrophages immune pathways dominated.Conclusion: Thus, the response of different cell-types with an identical genome exposed to the same stress of smoking is different; responses of alveolar macrophages are more subdued than those of airway epithelium. These findings are consistent with the observation that, while the small airway epithelium is vulnerable, alveolar macrophages are not "diseased" in response to smoking.Trial Registration: ClinicalTrials.gov ID: NCT00224185 and NCT00224198.

UR - http://www.scopus.com/inward/record.url?scp=73949085683&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73949085683&partnerID=8YFLogxK

U2 - 10.1186/1465-9921-10-111

DO - 10.1186/1465-9921-10-111

M3 - Article

VL - 10

JO - Respiratory Research

JF - Respiratory Research

SN - 1465-9921

M1 - 111

ER -