BACKGROUND: We have previously reported gene expression changes in the bronchial airway epithelium of active chronic smokers. In this study, we investigate the effects of Acute Smoke Exposure (ASE) from cigarettes on airway epithelial gene expression. METHODS: Bronchial airway epithelial cell brushings were collected via fiberoptic bronchoscopy from 63 individuals without recent exposure to cigarette smoke (> 2 days), at baseline and at 24 hours after smoking three cigarettes. RNA from these samples was profiled on Affymetrix Human Gene 1.0 ST microarrays. Differential gene expression was assessed using linear modeling and compared to previous smoking-related gene-expression signatures using Gene Set Enrichment Analysis (GSEA). RESULTS: We identified 91 genes differentially expressed 24-hours after exposure to three cigarettes (FDR < 0.25). ASE induces genes involved in xenobiotic metabolism, oxidative stress, and inflammation; and represses genes involved in cilium morphogenesis, and cell cycle. Genes induced by in vivo ASE are concordantly altered by ASE in vitro. While many genes altered by ASE are altered similarly in the airway of chronic smokers, metallothionein genes were induced by ASE and suppressed among chronic smokers. Metallothioneins were also suppressed in the bronchial airway of current and former chronic smokers with lung cancer relative to those with benign disease. CONCLUSIONS: Acute exposure to as little as three cigarettes alters gene-expression in bronchial airway epithelium in a manner that largely resembles the changes seen in chronic active smokers. The difference in the short-term and long-term effects of smoking on metallothionein expression and its relationship to lung cancer requires further study given these enzymes role in responding to oxidative stress.
Impact of acute exposure to cigarette smoke on airway gene expression.
Sex
View SamplesA chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, double-blind, placebo controlled study in current heavy smokers to compare modulating effects of intermittent versus continuous low dose ASA on gene signatures of smoking and lung cancer from nasal brushings. Fifty-four participants were randomized to intermittent ASA (ASA 81 mg daily for one week alternating with placebo daily for one week) or continuous ASA (81 mg daily) for 12 weeks. The primary endpoint was modulation of a smoking gene signature in nasal brushings. Other [JB1] endpoints included modulation of nasal and bronchial gene signatures for smoking, lung cancer and chronic obstructive pulmonary disease (COPD) and changes in cyclooxygenase (COX)- and 5-lipoxygenase (LOX)-mediated arachidonic acid (ARA) metabolism.
Effect of Intermittent Versus Continuous Low-Dose Aspirin on Nasal Epithelium Gene Expression in Current Smokers: A Randomized, Double-Blinded Trial.
Sex, Age, Subject, Time
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Emergence of a stage-dependent human liver disease signature with directed differentiation of alpha-1 antitrypsin-deficient iPS cells.
Cell line
View SamplesWnt signaling pathway is thought to have a role in skin fibrosis in Systemic slcerosis. This Randomized, Placebo-Controlled trial examines the effect of beta catenin inhibition on skin expression.
Inhibition of β-Catenin Signaling in the Skin Rescues Cutaneous Adipogenesis in Systemic Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Trial of C-82.
Treatment, Time
View SamplesSystemic sclerosis is associated with skin fibrosis thought mediated by TGFb. This open label clinical trial examines the effect of TGFb inhibition on skin gene expression.
No associated publication
Treatment
View SamplesGene expression in histologically normal epithelium from breast cancer patients and cancer-free prophylactic mastectomy patients share a similar profile
Gene expression in histologically normal epithelium from breast cancer patients and from cancer-free prophylactic mastectomy patients shares a similar profile.
Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
miR-155 in the progression of lung fibrosis in systemic sclerosis.
Specimen part, Disease
View SamplesEach total RNA sample is hybridized to two different arrays: Affymetrix U133A (GPL96) and U133B (GPL97).
Previously unidentified changes in renal cell carcinoma gene expression identified by parametric analysis of microarray data.
No sample metadata fields
View SamplesWe used microarrays to explore gene expression in Systemic Sclerosis patients.
No associated publication
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Hepatocyte-specific mutation of both NF-κB RelA and STAT3 abrogates the acute phase response in mice.
Specimen part
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