Intranasally administered serelaxin abrogates airway remodelling and attenuates airway hyperresponsiveness in allergic airways disease

Simon G Royce, Clarice Lim, Krupesh P Patel, Bo Wang, Chrishan S Samuel, Mimi L K Tang

Research output: Contribution to journalArticleResearchpeer-review

20 Citations (Scopus)

Abstract

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 anti-remodeling effects. Serelaxin (a recombinant form of human gene-2 relaxin) has been shown to inhibit lung fibrosis in various disease models and reverse airway remodeling 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 remodeling and AHR associated with AAD. METHODS: Female Balb/c mice were subjected to a 9-week model of chronic AAD. Sub-groups of animals (n=12/group) were then treated intranasally with serelaxin (0.8mg/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 BAL cell counts, OVA-specific IgE levels, tissue inflammation, parameters of airway remodeling 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-beta1 expression, epithelial Smad2 phosphorylation (pSmad2), subepithelial collagen thickness, total lung collagen concentration and AHR (all p
Original languageEnglish
Pages (from-to)1399 - 1408
Number of pages10
JournalClinical and Experimental Allergy
Volume44
Issue number11
DOIs
Publication statusPublished - 2014

Cite this

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title = "Intranasally administered serelaxin abrogates airway remodelling and attenuates airway hyperresponsiveness in allergic airways disease",
abstract = "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 anti-remodeling effects. Serelaxin (a recombinant form of human gene-2 relaxin) has been shown to inhibit lung fibrosis in various disease models and reverse airway remodeling 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 remodeling and AHR associated with AAD. METHODS: Female Balb/c mice were subjected to a 9-week model of chronic AAD. Sub-groups of animals (n=12/group) were then treated intranasally with serelaxin (0.8mg/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 BAL cell counts, OVA-specific IgE levels, tissue inflammation, parameters of airway remodeling 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-beta1 expression, epithelial Smad2 phosphorylation (pSmad2), subepithelial collagen thickness, total lung collagen concentration and AHR (all p",
author = "Royce, {Simon G} and Clarice Lim and Patel, {Krupesh P} and Bo Wang and Samuel, {Chrishan S} and Tang, {Mimi L K}",
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Intranasally administered serelaxin abrogates airway remodelling and attenuates airway hyperresponsiveness in allergic airways disease. / Royce, Simon G; Lim, Clarice; Patel, Krupesh P; Wang, Bo; Samuel, Chrishan S; Tang, Mimi L K.

In: Clinical and Experimental Allergy, Vol. 44, No. 11, 2014, p. 1399 - 1408.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Intranasally administered serelaxin abrogates airway remodelling and attenuates airway hyperresponsiveness in allergic airways disease

AU - Royce, Simon G

AU - Lim, Clarice

AU - Patel, Krupesh P

AU - Wang, Bo

AU - Samuel, Chrishan S

AU - Tang, Mimi L K

PY - 2014

Y1 - 2014

N2 - 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 anti-remodeling effects. Serelaxin (a recombinant form of human gene-2 relaxin) has been shown to inhibit lung fibrosis in various disease models and reverse airway remodeling 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 remodeling and AHR associated with AAD. METHODS: Female Balb/c mice were subjected to a 9-week model of chronic AAD. Sub-groups of animals (n=12/group) were then treated intranasally with serelaxin (0.8mg/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 BAL cell counts, OVA-specific IgE levels, tissue inflammation, parameters of airway remodeling 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-beta1 expression, epithelial Smad2 phosphorylation (pSmad2), subepithelial collagen thickness, total lung collagen concentration and AHR (all p

AB - 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 anti-remodeling effects. Serelaxin (a recombinant form of human gene-2 relaxin) has been shown to inhibit lung fibrosis in various disease models and reverse airway remodeling 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 remodeling and AHR associated with AAD. METHODS: Female Balb/c mice were subjected to a 9-week model of chronic AAD. Sub-groups of animals (n=12/group) were then treated intranasally with serelaxin (0.8mg/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 BAL cell counts, OVA-specific IgE levels, tissue inflammation, parameters of airway remodeling 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-beta1 expression, epithelial Smad2 phosphorylation (pSmad2), subepithelial collagen thickness, total lung collagen concentration and AHR (all p

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