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The chitinase-like protein YKL-40 modulates cystic fibrosis lung disease

The chitinase-like protein YKL-40 was found to be increased in patients with severe asthma and chronic obstructive pulmonary disease (COPD), two disease conditions featuring neutrophilic infiltrates. Based on these studies and a previous report indicating that neutrophils secrete YKL-40, we hypothes...

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Main Authors: Hector, Andreas (Author) , Kormann, Michael (Author) , Mack, Ines (Author) , Latzin, Philipp (Author) , Casaulta, Carmen (Author) , Kieninger, Elisabeth (Author) , Zhou-Suckow, Zhe (Author) , Yildirim, Ali Ö (Author) , Bohla, Alexander (Author) , Rieber, Nikolaus (Author) , Kappler, Matthias (Author) , Koller, Barbara (Author) , Eber, Ernst (Author) , Eickmeier, Olaf (Author) , Zielen, Stefan (Author) , Eickelberg, Oliver (Author) , Griese, Matthias (Author) , Mall, Marcus A. (Author) , Hartl, Dominik (Author)
Format: Article (Journal)
Language:English
Published: September 20, 2011
In: PLOS ONE
Year: 2011, Volume: 6, Issue: 9, Pages: 1-6
ISSN:1932-6203
DOI:10.1371/journal.pone.0024399
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1371/journal.pone.0024399
Verlag, lizenzpflichtig, Volltext: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0024399
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Author Notes:Andreas Hector, Michael S. D. Kormann, Ines Mack, Philipp Latzin, Carmen Casaulta, Elisabeth Kieninger, Zhe Zhou, Ali Ö Yildirim, Alexander Bohla, Nikolaus Rieber, Matthias Kappler, Barbara Koller, Ernst Eber, Olaf Eickmeier, Stefan Zielen, Oliver Eickelberg, Matthias Griese, Marcus A. Mall, Dominik Hartl
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Summary:The chitinase-like protein YKL-40 was found to be increased in patients with severe asthma and chronic obstructive pulmonary disease (COPD), two disease conditions featuring neutrophilic infiltrates. Based on these studies and a previous report indicating that neutrophils secrete YKL-40, we hypothesized that YKL-40 plays a key role in cystic fibrosis (CF) lung disease, a prototypic neutrophilic disease. The aim of this study was (i) to analyze YKL-40 levels in human and murine CF lung disease and (ii) to investigate whether YKL-40 single-nucleotide polymorphisms (SNPs) modulate CF lung disease severity. YKL-40 protein levels were quantified in serum and sputum supernatants from CF patients and control individuals. Levels of the murine homologue BRP-39 were analyzed in airway fluids from CF-like βENaC-Tg mice. YKL-40SNPs were analyzed in CF patients. YKL-40 levels were increased in sputum supernatants and in serum from CF patients compared to healthy control individuals. Within CF patients, YKL-40 levels were higher in sputum than in serum. BRP-39 levels were increased in airways fluids from βENaC-Tg mice compared to wild-type littermates. In both CF patients and βENaC-Tg mice, YKL-40/BRP-39 airway levels correlated with the severity of pulmonary obstruction. Two YKL-40 SNPs (rs871799 and rs880633) were found to modulate age-adjusted lung function in CF patients. YKL-40/BRP-39 levelsare increased in human and murine CF airway fluids, correlate with pulmonary function and modulate CF lung disease severity genetically. These findings suggest YKL-40 as a potential biomarker in CF lung disease.
Item Description:Gesehen am 28.09.2022
Physical Description:Online Resource
ISSN:1932-6203
DOI:10.1371/journal.pone.0024399

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