title: Overexpression of chitinase 3-like 1/YKL-40 in lung-specific IL-18-transgenic mice, smokers and COPD.
abstract: We analyzed the lung mRNA expression profiles of a murine model of COPD developed using a lung-specific IL-18-transgenic mouse. In this transgenic mouse, the expression of 608 genes was found to vary more than 2-fold in comparison with control WT mice, and was clustered into 4 groups. The expression of 140 genes was constitutively increased at all ages, 215 genes increased gradually with aging, 171 genes decreased gradually with aging, and 82 genes decreased temporarily at 9 weeks of age. Interestingly, the levels of mRNA for the chitinase-related genes chitinase 3-like 1 (Chi3l1), Chi3l3, and acidic mammalian chitinase (AMCase) were significantly higher in the lungs of transgenic mice than in control mice. The level of Chi3l1 protein increased significantly with aging in the lungs and sera of IL-18 transgenic, but not WT mice. Previous studies have suggested Chi3l3 and AMCase are IL-13-driven chitinase-like proteins. However, IL-13 gene deletion did not reduce the level of Chi3l1 protein in the lungs of IL-18 transgenic mice. Based on our murine model gene expression data, we analyzed the protein level of YKL-40, the human homolog of Chi3l1, in sera of smokers and COPD patients. Sixteen COPD patients had undergone high resolution computed tomography (HRCT) examination. Emphysema was assessed by using a density mask with a cutoff of -950 Hounsfield units to calculate the low-attenuation area percentage (LAA%). We observed significantly higher serum levels in samples from 28 smokers and 45 COPD patients compared to 30 non-smokers. In COPD patients, there was a significant negative correlation between serum level of YKL-40 and %FEV(1). Moreover, there was a significant positive correlation between the serum levels of YKL-40 and LAA% in COPD patients. Thus our results suggest that chitinase-related genes may play an important role in establishing pulmonary inflammation and emphysematous changes in smokers and COPD patients.
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sakazaki
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
authors.forename: Satoko
authors.initials: S
authors.lastname: Takei
authors.forename: Masanori
authors.initials: M
authors.lastname: Sawada
authors.forename: Hanako
authors.initials: H
authors.lastname: Oda
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Takenaka
authors.forename: Haruki
authors.initials: H
authors.lastname: Imaoka
authors.forename: Kazuko
authors.initials: K
authors.lastname: Matsunaga
authors.forename: Toshio
authors.initials: T
authors.lastname: Ota
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Abe
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miki
authors.forename: Kiminori
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Kawayama
authors.forename: Seiya
authors.initials: S
authors.lastname: Kato
authors.forename: Hisamichi
authors.initials: H
authors.lastname: Aizawa
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000071451:Chitinase-3-Like Protein 1; D002688:Chitinases / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000378:metabolism*; D012129:Respiratory Function Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000235:genetics
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D016326:Extracellular Matrix Proteins; D018793:Interleukin-13; D020382:Interleukin-18; D037102:Lectins; C499254:CHIA protein, human; D002688:Chitinases