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

Pinkerton, JW; Kim, RY; Koeninger, L; Armbruster, NS; Hansbro, NG; Brown, AC; Jayaraman, R; Shen, S; Malek, N; Cooper, MA; Nordkild, P; Horvat, JC; Jensen, BAH; Wehkamp, J; Hansbro, PM

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

Pinkerton, JW Kim, RY Koeninger, L Armbruster, NS Hansbro, NG Brown, AC Jayaraman, R Shen, S

Malek, N Cooper, MA Nordkild, P Horvat, JC Jensen, BAH Wehkamp, J Hansbro, PM

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Publisher:: WILEY
Publication Type:: Journal Article
Citation:: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 2020
Issue Date:: 2020-10-23

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Field	Value	Language
dc.contributor.author	Pinkerton, JW
dc.contributor.author	Kim, RY
dc.contributor.author	Koeninger, L
dc.contributor.author	Armbruster, NS
dc.contributor.author	Hansbro, NG
dc.contributor.author	Brown, AC
dc.contributor.author	Jayaraman, R
dc.contributor.author	Shen, S https://orcid.org/0000-0002-1004-1936
dc.contributor.author	Malek, N
dc.contributor.author	Cooper, MA
dc.contributor.author	Nordkild, P
dc.contributor.author	Horvat, JC
dc.contributor.author	Jensen, BAH
dc.contributor.author	Wehkamp, J
dc.contributor.author	Hansbro, PM
dc.date.accessioned	2020-12-16T00:40:55Z
dc.date.available	2020-10-03
dc.date.available	2020-12-16T00:40:55Z
dc.date.issued	2020-10-23
dc.identifier.citation	Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 2020
dc.identifier.issn	0954-7894
dc.identifier.issn	1365-2222
dc.identifier.uri	http://hdl.handle.net/10453/144735
dc.description.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.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	WILEY
dc.relation	http://purl.org/au-research/grants/nhmrc/GNT1079187
dc.relation	http://purl.org/au-research/grants/nhmrc/1179092
dc.relation	http://purl.org/au-research/grants/nhmrc/1175134
dc.relation.ispartof	Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
dc.relation.isbasedon	10.1111/cea.13766
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	1107 Immunology, 1111 Nutrition and Dietetics, 1117 Public Health and Health Services
dc.subject.classification	Allergy
dc.title	Human β-defensin-2 suppresses key features of asthma in murine models of allergic airways disease.
dc.type	Journal Article
utslib.location.activity	England
utslib.for	1107 Immunology
utslib.for	1111 Nutrition and Dietetics
utslib.for	1117 Public Health and Health Services
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	closed_access	*
dc.date.updated	2020-12-16T00:40:44Z
pubs.publication-status	Published

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.

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http://hdl.handle.net/10453/144735