title: The chitinase-like proteins breast regression protein-39 and YKL-40 regulate hyperoxia-induced acute lung injury.
abstract: BACKGROUND
  Prolonged exposure to 100% O(2) causes hyperoxic acute lung injury (HALI), characterized by alveolar epithelial cell injury and death. We previously demonstrated that the murine chitinase-like protein, breast regression protein (BRP)-39 and its human homolog, YKL-40, inhibit cellular apoptosis. However, the regulation and roles of these molecules in hyperoxia have not been addressed.
  
  
  OBJECTIVE
  We hypothesized that BRP-39 and YKL-40 (also called chitinase-3-like 1) play important roles in the pathogenesis of HALI.
  
  
  METHODS
  We characterized the regulation of BRP-39 during HALI and the responses induced by hyperoxia in wild-type mice, BRP-39-null (-/-) mice, and BRP-39(-/-) mice in which YKL-40 was overexpressed in respiratory epithelium. We also compared the levels of tracheal aspirate YKL-40 in premature newborns with respiratory failure.
  
  
  RESULTS
  These studies demonstrate that hyperoxia inhibits BRP-39 in vivo in the murine lung and in vitro in epithelial cells. They also demonstrate that BRP-39(-/-) mice have exaggerated permeability, protein leak, oxidation, inflammatory, chemokine, and epithelial apoptosis responses, and experience premature death in 100% O(2). Lastly, they demonstrate that YKL-40 ameliorates HALI, prolongs survival in 100% O(2), and rescues the exaggerated injury response in BRP-39(-/-) animals. In accord with these findings, the levels of tracheal aspirate YKL-40 were lower in premature infants treated with hyperoxia for respiratory failure who subsequently experienced bronchopulmonary dysplasia or death compared with those that did not experience these complications.
  
  
  CONCLUSIONS
  These studies demonstrate that hyperoxia inhibits BRP-39/YKL-40, and that BRP-39 and YKL-40 are critical regulators of oxidant injury, inflammation, and epithelial apoptosis in the murine and human lung.
authors.affiliation: Department of Pediatrics, and Institute of Allergy, Severance Biomedical Science Institute, BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Myung Hyun
authors.initials: MH
authors.lastname: Sohn
authors.forename: Min-Jong
authors.initials: MJ
authors.lastname: Kang
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuura
authors.forename: Vineet
authors.initials: V
authors.lastname: Bhandari
authors.forename: Ning-Yuan
authors.initials: NY
authors.lastname: Chen
authors.forename: Chun Geun
authors.initials: CG
authors.lastname: Lee
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
mesh_terms: D055371:Acute Lung Injury / Q000503:physiopathology*; D054392:Adipokines; D000818:Animals; D017209:Apoptosis; D001997:Bronchopulmonary Dysplasia / Q000503:physiopathology*; D002478:Cells, Cultured; D000071451:Chitinase-3-Like Protein 1; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D018496:Hyperoxia / Q000503:physiopathology*; D007231:Infant, Newborn; D007234:Infant, Premature; D007249:Inflammation; D037102:Lectins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020545:Respiratory Mucosa / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; C509289:Chil1 protein, mouse; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins