- Title
- Human beta-defensin-2 suppresses key features of asthma in murine models of allergic airways disease
- Creator
- Pinkerton, James W.; Kim, Richard Y.; Nordkild, Peter; Horvat, Jay C.; Jensen, Benjanim A. H.; Wehkamp, Jan; Hansbro, Philip M.; Koeninger, Louis; Armbruster, Nicole S.; Hansbro, Nicole G.; Brown, Alexandra C.; Jayaraman, Ranjith; Shen, Sijie; Malek, Nisar; Cooper, Matthew A.
- Relation
- NHMRC.1079187 http://purl.org/au-research/grants/nhmrc/1079187
- Relation
- Clinical and Experimental Allergy Vol. 51, Issue 1, p. 120-131
- Publisher Link
- http://dx.doi.org/10.1111/cea.13766
- Publisher
- Wiley-Blackwell
- Resource Type
- journal article
- Date
- 2020
- Description
- 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.
- Subject
- asthma; steroid sensitive; steroid resistant; human β-defensin-2; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1441835
- Identifier
- uon:41553
- Identifier
- ISSN:0954-7894
- Language
- eng
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