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Inhibition of airway remodeling in IL-5–deficient mice
Jae Youn Cho, … , Stephanie Friedman, David H. Broide
Jae Youn Cho, … , Stephanie Friedman, David H. Broide
Published February 15, 2004
Citation Information: J Clin Invest. 2004;113(4):551-560. https://doi.org/10.1172/JCI19133.
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Article Pulmonology Article has an altmetric score of 3

Inhibition of airway remodeling in IL-5–deficient mice

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Abstract

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, α-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-β. 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-β, suggesting that eosinophils are a significant source of TGF-β in the remodeled airway. OVA challenge induced significantly higher levels of airway epithelial αVβ6 integrin expression, as well as significantly higher levels of bioactive lung TGF-β in WT compared with IL-5–deficient mice. Increased airway epithelial expression of αVβ6 integrin may contribute to the increased activation of latent TGF-β. These results suggest an important role for IL-5, eosinophils, αVβ6, and TGF-β in airway remodeling.

Authors

Jae Youn Cho, Marina Miller, Kwang Je Baek, Ji Won Han, Jyothi Nayar, Sook Young Lee, Kirsti McElwain, Shauna McElwain, Stephanie Friedman, David H. Broide

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Figure 6

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Expression of airway epithelial integrin αVβ6 in WT and IL-5 KO mice. Ne...
Expression of airway epithelial integrin αVβ6 in WT and IL-5 KO mice. Neither non–OVA-challenged WT mice (a) nor non–OVA-challenged IL-5–deficient mice (b) had significant numbers of airway epithelial cells that immunostained positive for αVβ6. In contrast, WT mice challenged repetitively with OVA for 3 months had a significant increase in the number of airway epithelial cells that immunostained positive for αVβ6 (c). There was a significant reduction in IL-5–deficient mice in the number of airway epithelial cells that immunostain positive for αVβ6 following repetitive OVA challenge (d). Quantitative analysis of αVβ6 integrin expression in airway epithelial cells demonstrated that repetitive OVA challenge in WT mice induced a significant increase in αVβ6 expression in WT mice compared with diluent-challenged WT mice (WT OVA versus WT no OVA; P < 0.001). The area of airway epithelium staining positively for αVβ6 in repetitively OVA-challenged IL-5–deficient mice was significantly less than that of repetitively OVA-challenged WT mice (IL-5 KO OVA versus WT OVA) (P < 0.001) (e).

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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