Human β‐defensin‐2 suppresses key features of asthma in murine models of allergic airways disease

Human β‐defensin‐2 suppresses key features of asthma in murine models of allergic airways disease.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1111/cea.13766
Journal or Publication Title: Clinical & Experimental Allergy
Date: 2020
Divisions: UTS Centre for Inflammation
Depositing User: General Admin
Identification Number: 10.1111/cea.13766
ISSN: 0954-7894
Date Deposited: 03 Jan 2021 23:51
Abstract:

Background
Asthma is an airway inflammatory disease and a major health problem worldwide. Anti‐inflammatory steroids and bronchodilators are the gold‐standard therapy for asthma. However, they do not prevent the development of the disease, and critically, a subset of asthmatics are resistant to steroid therapy.

Objective
To elucidate the therapeutic potential of human β‐defensins (hBD), such as hBD2 mild to moderate and severe asthma.

Methods
We investigated the role of hBD2 in a steroid‐sensitive, house dust mite‐induced allergic airways disease (AAD) model and a steroid‐insensitive model combining ovalbumin‐induced AAD with C muridarum (Cmu) respiratory infection.

Results
In both models, we demonstrated that therapeutic intranasal application of hBD2 significantly reduced the influx of inflammatory cells into the bronchoalveolar lavage fluid. Furthermore, key type 2 asthma‐related cytokines IL‐9 and IL‐13, as well as additional immunomodulating cytokines, were significantly decreased after administration of hBD2 in the steroid‐sensitive model. The suppression of inflammation was associated with improvements in airway physiology and treatment also suppressed airway hyper‐responsiveness (AHR) in terms of airway resistance and compliance to methacholine challenge.

Conclusions and Clinical relevance
These data indicate that hBD2 reduces the hallmark features and has potential as a new therapeutic agent in allergic and especially steroid‐resistant asthma.

Creators:
Creators
Email
Pinkerton, James W.
UNSPECIFIED
Kim, Richard Y.
UNSPECIFIED
Koeninger, Louis
UNSPECIFIED
Armbruster, Nicole S.
UNSPECIFIED
Hansbro, Nicole G.
UNSPECIFIED
Brown, Alexandra C.
UNSPECIFIED
Jayaraman, Ranjith
UNSPECIFIED
Shen, Sijie
UNSPECIFIED
Malek, Nisar
UNSPECIFIED
Cooper, Matthew A.
UNSPECIFIED
Nordkild, Peter
UNSPECIFIED
Horvat, Jay C.
UNSPECIFIED
Jensen, Benjamin A. H.
UNSPECIFIED
Wehkamp, Jan
UNSPECIFIED
Hansbro, Philip M.
UNSPECIFIED
Last Modified: 03 Jan 2021 23:51
URI: https://eprints.centenary.org.au/id/eprint/835

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