Inhibition of airway remodeling in IL-5-deficient mice

被引:319
作者
Cho, JY [1 ]
Miller, M [1 ]
Baek, KJ [1 ]
Han, JW [1 ]
Nayar, J [1 ]
Lee, SY [1 ]
McElwain, K [1 ]
McElwain, S [1 ]
Friedman, S [1 ]
Broide, DH [1 ]
机构
[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
关键词
D O I
10.1172/JCI200419133
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
To determine the role of IL-5 in airway remodeling, IL-5-deficient and WT mice were sensitized to OVA and challenged by repetitive administration of OVA for 3 months. IL-5-deficient mice had significantly less peribronchial fibrosis (total lung collagen content, peribronchial collagens III and V) and significantly less peribronchial smooth muscle (thickness of peribronchial smooth muscle layer, alpha-smooth muscle actin immunostaining) compared with WT mice challenged with OVA. WT mice had a significant increase in the number of peribronchial cells staining positive for major basic protein and TGF-beta. In contrast, IL-5-deficient mice had a significant reduction in the number of peribronchial cells staining positive for major basic protein, which was paralleled by a similar reduction in the number of cells staining positive for TGF-beta, suggesting that eosinophils are a significant source of TGF-beta in the remodeled airway. OVA challenge induced significantly higher levels of airway epithelial alpha(V)beta(6) integrin expression, as well as significantly higher levels of bioactive lung TGF-beta in WT compared with IL-5-deficient mice. Increased airway epithelial. expression Of alpha(V)beta(6) integrin may contribute to the increased activation of latent TGF-beta. These results suggest an important role for IL-5, eosinophils, alpha(V)beta(6), and TGF-beta in airway remodeling.
引用
收藏
页码:551 / 560
页数:10
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