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Increased Expression of Beta-Defensin 1 (DEFB1) in Chronic Obstructive Pulmonary Disease

On-going airway inflammation is characteristic for the pathophysiology of chronic obstructive pulmonary disease (COPD). However, the key factors determining the decrease in lung function, an important clinical parameter of COPD, are not clear. Genome-wide linkage analyses provide evidence for signif...

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Autores principales: Andresen, Ellen, Günther, Gunar, Bullwinkel, Jörn, Lange, Christoph, Heine, Holger
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139569/
https://www.ncbi.nlm.nih.gov/pubmed/21818276
http://dx.doi.org/10.1371/journal.pone.0021898
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author Andresen, Ellen
Günther, Gunar
Bullwinkel, Jörn
Lange, Christoph
Heine, Holger
author_facet Andresen, Ellen
Günther, Gunar
Bullwinkel, Jörn
Lange, Christoph
Heine, Holger
author_sort Andresen, Ellen
collection PubMed
description On-going airway inflammation is characteristic for the pathophysiology of chronic obstructive pulmonary disease (COPD). However, the key factors determining the decrease in lung function, an important clinical parameter of COPD, are not clear. Genome-wide linkage analyses provide evidence for significant linkage to airway obstruction susceptibility loci on chromosome 8p23, the location of the human defensin gene cluster. Moreover, a genetic variation in the defensin beta 1 (DEFB1) gene was found to be associated with COPD. Therefore, we hypothesized that DEFB1 is differently regulated and expressed in human lungs during COPD progression. Gene expression of DEFB1 was assessed in bronchial epithelium and BAL fluid cells of healthy controls and patients with COPD and using bisulfite sequencing and ChIP analysis, the epigenetic control of DEFB1 mRNA expression was investigated. We can demonstrate that DEFB1 mRNA expression was significantly increased in bronchopulmonary specimen of patients with COPD (n = 34) vs. healthy controls (n = 10) (p<0.0001). Furthermore, a significant correlation could be detected between DEFB1 and functional parameters such as FEV(1) (p = 0.0024) and the FEV(1)/VC ratio (p = 0.0005). Upregulation of DEFB1 mRNA was paralleled by changes in HDAC1-3, HDAC5 and HDAC8 mRNA expression. Whereas bisulfite sequencing revealed no differences in the methylation state of DEFB1 promoter between patients with COPD and controls, ChIP analysis showed that enhanced DEFB1 mRNA expression was associated with the establishment of an active histone code. Thus, expression of human DEFB1 is upregulated and related to the decrease in pulmonary function in patients with COPD.
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spelling pubmed-31395692011-08-04 Increased Expression of Beta-Defensin 1 (DEFB1) in Chronic Obstructive Pulmonary Disease Andresen, Ellen Günther, Gunar Bullwinkel, Jörn Lange, Christoph Heine, Holger PLoS One Research Article On-going airway inflammation is characteristic for the pathophysiology of chronic obstructive pulmonary disease (COPD). However, the key factors determining the decrease in lung function, an important clinical parameter of COPD, are not clear. Genome-wide linkage analyses provide evidence for significant linkage to airway obstruction susceptibility loci on chromosome 8p23, the location of the human defensin gene cluster. Moreover, a genetic variation in the defensin beta 1 (DEFB1) gene was found to be associated with COPD. Therefore, we hypothesized that DEFB1 is differently regulated and expressed in human lungs during COPD progression. Gene expression of DEFB1 was assessed in bronchial epithelium and BAL fluid cells of healthy controls and patients with COPD and using bisulfite sequencing and ChIP analysis, the epigenetic control of DEFB1 mRNA expression was investigated. We can demonstrate that DEFB1 mRNA expression was significantly increased in bronchopulmonary specimen of patients with COPD (n = 34) vs. healthy controls (n = 10) (p<0.0001). Furthermore, a significant correlation could be detected between DEFB1 and functional parameters such as FEV(1) (p = 0.0024) and the FEV(1)/VC ratio (p = 0.0005). Upregulation of DEFB1 mRNA was paralleled by changes in HDAC1-3, HDAC5 and HDAC8 mRNA expression. Whereas bisulfite sequencing revealed no differences in the methylation state of DEFB1 promoter between patients with COPD and controls, ChIP analysis showed that enhanced DEFB1 mRNA expression was associated with the establishment of an active histone code. Thus, expression of human DEFB1 is upregulated and related to the decrease in pulmonary function in patients with COPD. Public Library of Science 2011-07-19 /pmc/articles/PMC3139569/ /pubmed/21818276 http://dx.doi.org/10.1371/journal.pone.0021898 Text en Andresen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Andresen, Ellen
Günther, Gunar
Bullwinkel, Jörn
Lange, Christoph
Heine, Holger
Increased Expression of Beta-Defensin 1 (DEFB1) in Chronic Obstructive Pulmonary Disease
title Increased Expression of Beta-Defensin 1 (DEFB1) in Chronic Obstructive Pulmonary Disease
title_full Increased Expression of Beta-Defensin 1 (DEFB1) in Chronic Obstructive Pulmonary Disease
title_fullStr Increased Expression of Beta-Defensin 1 (DEFB1) in Chronic Obstructive Pulmonary Disease
title_full_unstemmed Increased Expression of Beta-Defensin 1 (DEFB1) in Chronic Obstructive Pulmonary Disease
title_short Increased Expression of Beta-Defensin 1 (DEFB1) in Chronic Obstructive Pulmonary Disease
title_sort increased expression of beta-defensin 1 (defb1) in chronic obstructive pulmonary disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139569/
https://www.ncbi.nlm.nih.gov/pubmed/21818276
http://dx.doi.org/10.1371/journal.pone.0021898
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