Inhibition of airway remodeling in IL-5–deficient mice
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
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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Article Pulmonology

Inhibition of airway remodeling in IL-5–deficient mice

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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Quantitation of peribronchial fibrosis in WT and IL-5–deficient mice rep...
Quantitation of peribronchial fibrosis in WT and IL-5–deficient mice repetitively challenged with OVA. (a) Area of peribronchial trichrome stain. WT mice repetitively challenged with OVA for 3 months developed an increased area of peribronchial trichrome staining compared with non–OVA-challenged WT mice (*WT OVA versus WT no OVA; P < 0.001). In contrast, IL-5–deficient mice repetitively challenged with OVA for 3 months had significantly reduced areas of peribronchial trichrome staining compared with WT mice repetitively challenged with OVA for 3 months (**IL-5 KO OVA versus WT OVA; P < 0.001). (b) Total lung collagen content. Repetitive OVA challenge induced a significant increase in total lung collagen in WT mice (#WT OVA versus WT no OVA; P < 0.001). IL-5–deficient mice repetitively challenged with OVA had less total lung collagen compared with WT mice repetitively challenged with OVA (##IL-5 KO OVA versus WT OVA; P < 0.05). (c) Collagen III and (d) collagen V lung immunostaining. WT mice repetitively challenged with OVA for 3 months developed increased peribronchial collagen III immunostaining (†WT OVA versus WT no OVA; P < 0.001) (c), as well as increased peribronchial collagen V immunostaining compared with non-OVA–challenged WT mice (§WT OVA versus WT no OVA; P < 0.001) (d). In contrast, IL-5–deficient mice repetitively challenged with OVA had significantly reduced levels of peribronchial collagen III immunostaining (††IL-5 KO OVA versus WT OVA; P < 0.001) (c), as well as significantly reduced levels of peribronchial collagen V immunostaining, compared with WT mice challenged repetitively with OVA for 3 months (§§IL-5 KO OVA versus WT OVA; P < 0.001) (d).