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Hector, A.* ; Kormann, M.S.* ; Mack, I.* ; Latzin, P.* ; Casaulta, C.* ; Kieninger, E.* ; Zhou, Z.* ; Yildirim, A.Ö. ; Bohla, A. ; Rieber, N.* ; Kappler, M.* ; Koller, B.* ; Eber, E.* ; Eickmeier, O.* ; Zielen, S.* ; Eickelberg, O. ; Griese, M.* ; Mall, M.A.* ; Hartl, D.*

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

PLoS ONE 6:e24399 (2011)
Publ. Version/Full Text Volltext DOI
Open Access Gold
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords MAMMALIAN MEMBER; SEVERE ASTHMA; SERUM-LEVELS; NEUTROPHILS; INFLAMMATION; CELLS; IDENTIFICATION; MACROPHAGES; INVOLVEMENT; EXPRESSION
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 6, Issue: 9, Pages: , Article Number: e24399 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Reviewing status Peer reviewed