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)
    
    
    
      
      
	
	    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
    
 
    
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        Keywords
        MAMMALIAN MEMBER; SEVERE ASTHMA; SERUM-LEVELS; NEUTROPHILS; INFLAMMATION; CELLS; IDENTIFICATION; MACROPHAGES; INVOLVEMENT; EXPRESSION
    
 
    
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        Language
        english
    
 
    
        Publication Year
        2011
    
 
    
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        2011
    
 
    
    
        ISSN (print) / ISBN
        1932-6203
    
 
    
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	    Volume: 6,  
	    Issue: 9,  
	    Pages: ,  
	    Article Number: e24399 
	    Supplement: ,  
	
    
 
    
        
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            Publisher
            Public Library of Science (PLoS)
        
 
        
            Publishing Place
            Lawrence, Kan.
        
 
	
        
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        Reviewing status
        Peer reviewed
    
 
     
    
        POF-Topic(s)
        30202 - Environmental Health
    
 
    
        Research field(s)
        Lung Research
    
 
    
        PSP Element(s)
        G-501600-001
G-505000-007
    
 
    
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        Erfassungsdatum
        2011-11-07