Usage Information

Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life
Elizabeth R. Davies, Joanne F.C. Kelly, Peter H. Howarth, David I. Wilson, Stephen T. Holgate, Donna E. Davies, Jeffrey A. Whitsett, Hans Michael Haitchi
Elizabeth R. Davies, Joanne F.C. Kelly, Peter H. Howarth, David I. Wilson, Stephen T. Holgate, Donna E. Davies, Jeffrey A. Whitsett, Hans Michael Haitchi
View: Text | PDF
Research Article Pulmonology

Soluble ADAM33 initiates airway remodeling to promote susceptibility for allergic asthma in early life

Abstract

Asthma is a chronic inflammatory airways disease that usually begins in early life and involves gene-environment interactions. Although most asthma exhibits allergic inflammation, many allergic individuals do not have asthma. Here, we report how the asthma gene a disintegrin and metalloprotease 33 (ADAM33) acts as local tissue susceptibility gene that promotes allergic asthma. We show that enzymatically active soluble ADAM33 (sADAM33) is increased in asthmatic airways and plays a role in airway remodeling, independent of inflammation. Furthermore, remodeling and inflammation are both suppressed in Adam33-null mice after allergen challenge. When induced in utero or added ex vivo, sADAM33 causes structural remodeling of the airways, which enhances postnatal airway eosinophilia and bronchial hyperresponsiveness following subthreshold challenge with an aeroallergen. This substantial gene-environment interaction helps to explain the end-organ expression of allergic asthma in genetically susceptible individuals. Finally, we show that sADAM33-induced airway remodeling is reversible, highlighting the therapeutic potential of targeting ADAM33 in asthma.

Authors

Elizabeth R. Davies, Joanne F.C. Kelly, Peter H. Howarth, David I. Wilson, Stephen T. Holgate, Donna E. Davies, Jeffrey A. Whitsett, Hans Michael Haitchi

×

Usage data is cumulative from December 2024 through December 2025.

Usage JCI PMC
Text version 704 132
PDF 131 19
Figure 508 2
Supplemental data 47 3
Citation downloads 102 0
Totals 1,492 156
Total Views 1,648
(Click and drag on plot area to zoom in. Click legend items above to toggle)

Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.

Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.

Advertisement