Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human isolated alveolar macrophages reveals an activation state associated with smoking

ABSTRACT: This series represents isolated alveolar macrophages from human subjects.

ORGANISM(S): Homo sapiens

SUBMITTER: Michael Salazar

PROVIDER: E-GEOD-2125 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A distinctive alveolar macrophage activation state induced by cigarette smoking.

Woodruff Prescott G PG Koth Laura L LL Yang Yee Hwa YH Rodriguez Madeleine W MW Favoreto Silvio S Dolganov Gregory M GM Paquet Agnes C AC Erle David J DJ

American journal of respiratory and critical care medicine 20050915 11

<h4>Rationale</h4>Macrophages are believed to play a central role in emphysema based largely on data from mouse models. However, the relevance of these models to smoking-related lung disease in humans is uncertain.<h4>Objectives</h4>We sought to comprehensively characterize the effects of smoking on gene expression in human alveolar macrophages and to compare these with effects seen in transgenic mouse models of emphysema.<h4>Methods</h4>We used DNA microarrays with genomewide coverage to analyz ...[more]

PMID: 16166618

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Project description:The glutathione S-transferase (GST) gene family codes for enzymes that detoxify xenobiotics by catalyzing the conjugation of xenobiotics to glutathione. Based on reports that inherited copy number variations (CNV) in the genome modulate some GST expression levels and with the knowledge that cigarette smoke contains >3000 xenobiotics, and that the small airway epithelium and alveolar macrophages are involved early in the pathogensis of smoking-induced lung disease, we asked: do germline CNVs modulate GST expression level in the small airway epithelium and alveolar macrophages? Affymetrix HG U133 Plus 2.0 microarrays were used to survey GST gene expression in the small airway epithelium and alveolar macrophages obtained by bronchoscopic brushings from current smokers (n=35) and nonsmokers (n=35). The CNV genotypes of these 70 subjects were determined by Affymetrix Human SNP array 5.0 chips. Sixteen % of subjects had deletions of both GSTM1 alleles. These deletions were associated with reduced GSTM1 mRNA levels in both the small airway epithelium (p<10-7) and alveolar macrophages (p<0.05). Thirty % of subjects had homozygous deletions of GSTT1 with concomitant reduced mRNA levels in both small airway epithelium and alveolar macrophages (p<10-7). In contrast, genes flanking the CNV regions of both GST genes showed no difference in expression level among subjects with and without the GST deletions (p>0.3). Interestingly, GSTT2B, a duplicate gene of GSTT2, exhibited homozygous deletion in blood in 27% of subjects and was not expressed in small airway epithelium in the remainder of subjects but was expressed in alveolar macrophages of heterozygotes and wild type subjects, proportionate to genotype (p<10-3). These data demonstrate that highly prevalent CNV deletions of genes critical to ameliorating smoking-associated xenobiotic-induced damage in the lung can result in significant modulation of the gene expression levels, with the linear relationship of genotype to expression level suggesting minimal compensation of gene expression levels in heterozygotes consistent with GST polymorphisms playing a role in the risk for development of smoking-induced lung disease.

Dataset Information

Transcription profiling of human isolated alveolar macrophages reveals an activation state associated with smoking

Publications

A distinctive alveolar macrophage activation state induced by cigarette smoking.

Similar Datasets

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