Overexpression Of Chitinase 3-Like 1/YKL-40 In Lung-Specific IL-18-Transgenic Mice, Smokers And COPD

Abstract

In this study, we analyzed the lung mRNA expression profiles of murine model of COPD, lung-specific IL-18-transgenic mice using microarray analysis. In the IL-18-transgenic mice, the expression of 608 genes was found to fluctuate 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, that of 215 genes increased gradually with aging, that of 171 genes decreased gradually with aging, and that of 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 of IL-18 transgenic, but not WT mice. Previous studies have suggested that 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. Furthermore, the protein level of YKL-40, the human homolog of Chi3l1, was significantly (P 1 . Chitinase-related genes may play an import role in establishing pulmonary inflammation and emphysematous changes.