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

• Verfasst von: Hector, Andreas [VerfasserIn]
• Verfasst von: Kormann, Michael [VerfasserIn]
• Verfasst von: Mack, Ines [VerfasserIn]
• Verfasst von: Latzin, Philipp [VerfasserIn]
• Verfasst von: Casaulta, Carmen [VerfasserIn]
• Verfasst von: Kieninger, Elisabeth [VerfasserIn]
• Verfasst von: Zhou-Suckow, Zhe [VerfasserIn]
• Verfasst von: Yildirim, Ali Ö [VerfasserIn]
• Verfasst von: Bohla, Alexander [VerfasserIn]
• Verfasst von: Rieber, Nikolaus [VerfasserIn]
• Verfasst von: Kappler, Matthias [VerfasserIn]
• Verfasst von: Koller, Barbara [VerfasserIn]
• Verfasst von: Eber, Ernst [VerfasserIn]
• Verfasst von: Eickmeier, Olaf [VerfasserIn]
• Verfasst von: Zielen, Stefan [VerfasserIn]
• Verfasst von: Eickelberg, Oliver [VerfasserIn]
• Verfasst von: Griese, Matthias [VerfasserIn]
• Verfasst von: Mall, Marcus A. [VerfasserIn]
• Verfasst von: Hartl, Dominik [VerfasserIn]
• Titel: The chitinase-like protein YKL-40 modulates cystic fibrosis lung disease
• Verf.angabe: 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
• E-Jahr: 2011
• Jahr: September 20, 2011
• Umfang: 6 S.
• Illustrationen: Diagramme
• Fussnoten: Gesehen am 28.09.2022
• Titel Quelle: Enthalten in: PLOS ONE
• Ort Quelle: San Francisco, California, US : PLOS, 2006
• Jahr Quelle: 2011
• Band/Heft Quelle: 6(2011), 9 vom: Sept., Artikel-ID e24399, Seite 1-6
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0024399
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Asthma
• Sach-SW: Cystic fibrosis
• Sach-SW: Inflammatory diseases
• Sach-SW: Mouse models
• Sach-SW: Pulmonary function
• Sach-SW: Serum proteins
• Sach-SW: Single nucleotide polymorphisms
• Sach-SW: Sputum
• K10plus-PPN: 1817716867

Abstract

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.