Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Smoking is Associated with Shortened Airway Cilia

ABSTRACT: Background: Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting cilia length must exceed the 6 -7 μm airway surface fluid depth to generate force in the mucus layer, we hypothesized cilia height may be decreased in airway epithelium of normal smokers compared to nonsmokers. Methodology/Principal Findings: Cilia length in normal nonsmokers and smokers was evaluated in aldehyde-fixed, paraffin-embedded endobronchial biopsies, and air-dried and hydrated samples brushed from human airway epithelium via fiberoptic bronchoscopy. In 28 endobronchial biopsies, healthy smoker cilia length was reduced 15% compared to nonsmokers (p<0.05). In 47 air-dried samples of airway epithelial cells, smoker cilia length was reduced 13% compared to nonsmokers (p<0.0001). Analysis of the length of individual, detached cilia in 17 samples, smoker cilia length was reduced 9% compared to nonsmokers (p<0.05). Finally, in 16 fully hydrated, unfixed samples, smoker cilia length was reduced 7% compared to nonsmokers (p<0.05). Conclusions/significance: Models predict that a reduction in cilia length would reduce mucociliary clearance, suggesting that smoking-associated shorter airway epithelial cilia plays a significant role in the pathogenesis of smoking-induced lung disease.

ORGANISM(S): Homo sapiens

SUBMITTER: Yael Strulovici-Barel

PROVIDER: E-GEOD-16696 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

Smoking is associated with shortened airway cilia.

Leopold Philip L PL O'Mahony Michael J MJ Lian X Julie XJ Tilley Ann E AE Harvey Ben-Gary BG Crystal Ronald G RG

PloS one 20091216 12

<h4>Background</h4>Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting that cilia length must exceed the 6-7 microm airway surface fluid depth to generate force in the mucus layer, we hypothesized that cilia height may be decreased in airway epithelium of normal smokers compared to nonsmoke ...[more]

PMID: 20016779

Similar Datasets

Project description:Study Smoking and COPD are associated with decreased mucociliary clearance and healthy smokers have shorter cilia in the large airway than nonsmokers. Intraflagellar transport (IFT) is the process by which cilia are produced and maintained. We assessed expression of IFT-related genes in smokers and nonsmokers and evaluated cilia length in the large and small airway of nonsmokers, healthy smokers, and smokers with COPD. Methods Airway epithelium was obtained via bronchoscopic brushing. Affymetrix microarrays were used to evaluate IFT gene expression in 2 independent data sets from large and small airway. Cilia length was assessed by measuring 100 cilia (10 cilia on each of 10 cells) per subject. Results All 40 IFT genes were expressed in the human large and small airway epithelium. In the large airway, 10 IFT genes were down-regulated and 1 up-regulated in smokers. In the small airway, 11 genes were down-regulated and 3 up-regulated in smokers. A set of 8 IFT genes was down-regulated in both data sets. In the large and small airway epithelium, cilia were significantly shorter in healthy smokers than nonsmokers, and significantly shorter in COPD smokers than in both healthy smokers and nonsmokers. Answer to the Question These results support the concept that loss of cilia length contributes to defective mucociliary clearance in COPD, and that smoking-induced changes in expression of IFT genes may be one mechanism of abnormally short cilia in smokers. Strategies to normalize cilia length may be an important avenue for novel COPD therapies. Gene expression was assessed for 40 intraflagellar transport related genes in the LAE of nonsmokers (n=21) and healthy smokers (n=31) and the SAE of an independent group of nonsmokers (n=28) and healthy smokers (n=69). Cilia length was assessed in a total of 228 airway epithelium samples, including 120 LAE samples and 108 SAE samples; a subset of the 228 samples is represented among the 149 samples in this Series.

Project description:Lectins are proteins present on cell surfaces or as shed extracellular proteins that function in innate immune defense as phagocytic receptors to recognize specific bacterial cell wall components. Based on the knowledge that cigarette smoking is associated with increased risk of bacterial infection, we hypothesized that cigarette smoking may modulate the expression of lectin genes in the airway epithelium. Affymetrix HG U133 Plus 2.0 microarrays were used to survey expression of lectin genes in large (3rd to 4th order bronchi) airway epithelium from 9 normal nonsmokers and 20 phenotypic normal smokers and small (10th to 12th order bronchi) airway epithelium from 13 normal nonsmokers and 20 phenotypic normal smokers. From the 72 lectin genes that were surveyed, there were no changes (>2-fold change, p<0.05) in gene expression in either large or small airway epithelium among normal smokers compared to nonsmokers except for a striking down regulation in both large and small airway epithelium of normal smokers of intelectin 1, a recently described lectin that participates in the innate immune response by recognizing and binding to galactofuranosyl residues in the cell walls of bacteria (large airway epithelium, p<0.003; small airway epithelium, p<0.002). TaqMan RT-PCR confirmed the observation that intelectin 1 was down-regulated in both large (p<0.05) and small airway epithelium (p<0.02) of normal smokers compared to normal nonsmokers. Immunohistochemistry assessment of biopsies of the large airway epithelium of normal nonsmokers demonstrated intelectin 1 was expressed in secretory cells, with qualitatively decreased expression in biopsies from normal smokers. Western analysis confirmed the decreased expression of intelectin 1 in airway epithelium of normal smokers compared to normal nonsmokers (p<0.02). Finally, compared to normal nonsmokers, intelectin 1 expression was decreased in small airway epithelium of smokers with early COPD (n= 13, p<0.001) and smokers with established COPD (n= 14, p<0.001), in a fashion similar to that of normal smokers. In the context that intelectin 1 is an epithelial molecule that likely plays a role in defense against bacteria, the down regulation of expression of intelectin 1 in response to cigarette smoking may contribute to the increase in susceptibility to infections observed in smokers, including those with COPD. Keywords: COPD Comparison of gene expression in airway epithelial cells of normal non-smokers, phenotypic normal smokers, smokers with early COPD, and smokers with COPD.

Project description:The small airway epithelium (SAE) the pseudostratified epithelium that covers the majority of the human airway surface from the 6th generation to the alveoli, is the major site of lung disease caused by smoking, and the cell population that exhibits the earliest manifestations of smoking-induced disease. The focus of this study is to use RNA-Seq (massive parallel sequencing technology) to sequence all polyA+ mRNAs expressed by the SAE of healthy nonsmokers to gain new insights into the biology of the SAE, and how these cells respond to cigarette smoke. Taking advantage of RNA-Seq providing quantitative mRNA levels, that data demonstrates that while the SAE shares its transcriptome with many cell types, it has unique characteristics that are enriched in this cell population, with the mostly highly expressed genes (SCGB1A1) characteristics of Clara cells, an airway epithelial cell unique to the human small airways. Among other genes expressed by the SAE are those characteristic of ciliated and mucin-producing cells, basal cells and neuroendocrine cells. The RNA-Seq data includes identification of the highly expressed SAE transcription factors, transmembrane receptors, signaling ligands and growth factors. RNA-Seq permitted quantification of expression of highly homologous gene families, the absolute smoking-induced changes in SAE gene expression, including genes expressed at low levels, and assessment of the effect of smoking on SAE gene splicing. Together, these observations can serve as the baseline for assessment of the dysregulation of SAE gene expression in human airway disease. The small airway epithelium (SAE) is the major site of lung disease caused by smoking, and the cell population that exhibits the earliest manifestations of smoking-induced disease. This study used RNA-Seq to sequence all polyA+ mRNAs expressed by the SAE of 5 healthy nonsmokers to gain new insights into the biology of the SAE, and evaluate how these cells respond to cigarette smoke using 6 healthy smoker samples (SRA029282.1). Taking advantage of RNA-Seq providing quantitative mRNA levels, that data demonstrates that while the SAE shares its transcriptome with many cell types, it has unique characteristics that are enriched in this cell population. Coverage of RNA-Seq expression was also compared to the HG-U133 Plus 2.0 microarray expression of 27 previously published healthy nonsmoker samples presented here.

Dataset Information

Smoking is Associated with Shortened Airway Cilia

Publications

Smoking is associated with shortened airway cilia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets