Coordinated DNA methylation and gene expression changes in smoker alveolar macrophages: specific effects on VEGF receptor 1 expression

Robert A Philibert; Rory A Sears; Linda S Powers; Emma Nash; Thomas Bair; Alicia K Gerke; Ihab Hassan; Christie P Thomas; Thomas J Gross; Martha M Monick

doi:10.1189/jlb.1211632

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Coordinated DNA methylation and gene expression changes in smoker alveolar macrophages: specific effects on VEGF receptor 1 expression

Journal article

Open access

Peer reviewed

Coordinated DNA methylation and gene expression changes in smoker alveolar macrophages: specific effects on VEGF receptor 1 expression

Robert A Philibert, Rory A Sears, Linda S Powers, Emma Nash, Thomas Bair, Alicia K Gerke, Ihab Hassan, Christie P Thomas, Thomas J Gross and Martha M Monick

Journal of leukocyte biology, Vol.92(3), pp.621-631

09/2012

DOI: 10.1189/jlb.1211632

PMCID: PMC3427615

PMID: 22427682

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Abstract

Cigarette smoking is implicated in numerous diseases, including emphysema and lung cancer. The clinical expression of lung disease in smokers is not well explained by currently defined variations in gene expression or simple differences in smoking exposure. Alveolar macrophages play a critical role in the inflammation and remodeling of the lung parenchyma in smoking-related lung disease. Significant gene expression changes in alveolar macrophages from smokers have been identified. However, the mechanism for these changes remains unknown. One potential mechanism for smoking-altered gene expression is via changes in cytosine methylation in DNA regions proximal to gene-coding sequences. In this study, alveolar macrophage DNA from heavy smokers and never smokers was isolated and methylation status at 25,000 loci determined. We found differential methylation in genes from immune-system and inflammatory pathways. Analysis of matching gene expression data demonstrated a parallel enrichment for changes in immune-system and inflammatory pathways. A significant number of genes with smoking-altered mRNA expression had inverse changes in methylation status. One gene highlighted by this data was the FLT1, and further studies found particular up-regulation of a splice variant encoding a soluble inhibitory form of the receptor. In conclusion, chronic cigarette smoke exposure altered DNA methylation in specific gene promoter regions in human alveolar macrophages.

Bronchoalveolar Lavage Fluid

Smoking - adverse effects

Macrophages, Alveolar

Gene Expression - genetics

Humans

Male

Smoking - genetics

DNA Methylation - genetics

Vascular Endothelial Growth Factor Receptor-1 - biosynthesis

Reverse Transcriptase Polymerase Chain Reaction

Promoter Regions, Genetic - genetics

Smoking - metabolism

Adult

Female

Vascular Endothelial Growth Factor Receptor-1 - genetics

Details

Title: Subtitle: Coordinated DNA methylation and gene expression changes in smoker alveolar macrophages: specific effects on VEGF receptor 1 expression
Creators: Robert A Philibert - Departments of Psychiatry, The University of Iowa, Iowa City, IA, USA
Rory A Sears
Linda S Powers
Emma Nash
Thomas Bair
Alicia K Gerke
Ihab Hassan
Christie P Thomas
Thomas J Gross
Martha M Monick
Resource Type: Journal article
Publication Details: Journal of leukocyte biology, Vol.92(3), pp.621-631
DOI: 10.1189/jlb.1211632
PMID: 22427682
PMCID: PMC3427615
NLM abbreviation: J Leukoc Biol
ISSN: 0741-5400
eISSN: 1938-3673
Publisher: United States
Grant note: R01 MH080898 / NIMH NIH HHS P30 DA027827 / NIDA NIH HHS UL1RR024979 / NCRR NIH HHS R21 HL109589 / NHLBI NIH HHS R21HL109589 / NHLBI NIH HHS P30DA027827 / NIDA NIH HHS R01 DK090053 / NIDDK NIH HHS R01 HL079901 / NHLBI NIH HHS R01 HL096625 / NHLBI NIH HHS UL1 RR024979 / NCRR NIH HHS MH080898 / NIMH NIH HHS
Language: English
Date published: 09/2012
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Obstetrics and Gynecology; Internal Medicine
Record Identifier: 9983985903202771

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