TY - JOUR

T1 - Human beta-defensin-2 suppresses key features of asthma in murine models of allergic airways disease

AU - Pinkerton, James W.

AU - Kim, Richard Y.

AU - Koeninger, Louis

AU - Armbruster, Nicole S.

AU - Hansbro, Nicole G.

AU - Brown, Alexandra C.

AU - Jayaraman, Ranjith

AU - Shen, Sijie

AU - Malek, Nisar

AU - Cooper, Matthew A.

AU - Nordkild, Peter

AU - Horvat, Jay C.

AU - Jensen, Benjamin A. H.

AU - Wehkamp, Jan

AU - Hansbro, Philip M.

PY - 2021

Y1 - 2021

N2 - 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 beta-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.

AB - 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 beta-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.

KW - asthma

KW - steroid sensitive

KW - steroid resistant

KW - human &#946

KW - &#8208

KW - defensin&#8208

KW - 2

KW - INFLAMMATORY-BOWEL-DISEASE

KW - BETA-DEFENSINS

KW - ADAPTIVE IMMUNITY

KW - INFECTION

KW - EXPRESSION

KW - THERAPY

KW - PEPTIDES

KW - INNATE

KW - CELLS

KW - LUNG

U2 - 10.1111/cea.13766

DO - 10.1111/cea.13766

M3 - Journal article

C2 - 33098152

VL - 51

SP - 120

EP - 131

JO - Clinical Allergy

JF - Clinical Allergy

SN - 0954-7894

IS - 1

ER -