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Intranasally administered serelaxin abrogates airway remodelling and attenuates airway hyperresponsiveness in allergic airways disease
Author(s) -
Royce S. G.,
Lim C. X. F.,
Patel K. P.,
Wang B.,
Samuel C. S.,
Tang M. L. K.
Publication year - 2014
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12391
Subject(s) - medicine , bronchoalveolar lavage , relaxin , nasal administration , immunology , fibrosis , lung , receptor
Summary Background The peptide hormone relaxin plays a key role in the systemic hemodynamic and renovascular adaptive changes that occur during pregnancy, which is linked to its antiremodelling effects. Serelaxin (a recombinant form of human gene‐2 relaxin) has been shown to inhibit lung fibrosis in various disease models and reverse airway remodelling and airway hyperresponsiveness ( AHR ) in allergic airways disease ( AAD ). Objective Although continuous systemic delivery of exogenous serelaxin alleviates allergic fibrosis and AHR , more direct routes for administration into the lung have not been investigated. Thus, intranasal administration of serelaxin was evaluated for its ability to reverse airway remodelling and AHR associated with AAD . Methods Female Balb/c mice were subjected to a 9‐week model of chronic AAD . Subgroups of animals ( n = 12/group) were then treated intranasally with serelaxin (0.8 mg/mL) or vehicle once daily for 14 days (from weeks 9–11). Saline‐sensitized/challenged mice treated with intranasal saline served as additional controls. Differential bronchoalveolar lavage ( BAL ) cell counts, ovalbumin ( OVA )‐specific IgE levels, tissue inflammation, parameters of airway remodelling and AHR were then assessed. Results Chronic AAD was associated with significant increases in differential BAL cell counts, OVA‐specific IgE levels, inflammation, epithelial thickening, goblet cell metaplasia, TGF‐β1 expression, epithelial Smad2 phosphorylation ( pS mad2), subepithelial collagen thickness, total lung collagen concentration and AHR (all P < 0.05 vs. respective measurements from saline‐treated mice). Daily intranasal delivery of serelaxin significantly diminished AAD‐induced epithelial thickening, epithelial pS mad2, subepithelial and total lung collagen content (fibrosis) and AHR (all P < 0.05 vs. vehicle‐treated AAD mice). Conclusions and Clinical Relevance Intranasal delivery of serelaxin can effectively reduce airway remodelling and AHR , when administered once daily. Respirable preparations of serelaxin may have therapeutic potential for the prevention and/or reversal of established airway remodelling and AHR in asthma.