Relaxin reverses airway remodeling and airway dysfunction in allergic airways disease.
Mice deficient in the antifibrotic hormone relaxin develop structural changes in the airway that resemble airway remodeling, and demonstrate exaggerated remodeling changes in models of allergic airways disease (AAD). Relaxin expression in asthma has not been previously studied. We evaluated the efficacy of relaxin in the treatment of established airway remodeling in a mouse model of AAD. Relaxin expression in mouse AAD was also examined by immunohistochemistry and real-time PCR. BALB/c mice with established AAD were treated with relaxin or vehicle control (sc for 14 d), and effects on airway remodeling, airway inflammation, and airway hyperresponsiveness (AHR) were assessed. Relaxin expression was significantly reduced in the airways of mice with AAD compared with controls. Recombinant relaxin treatment in a mouse model of AAD reversed collagen deposition and epithelial thickening, and significantly improved AHR (all P < 0.05 vs. vehicle control), but did not influence airway inflammation or goblet cell hyperplasia. Relaxin treatment was associated with increased matrix metalloproteinase-2 levels, suggesting a possible mechanism for its antifibrotic effects. Endogenous relaxin expression is decreased in murine AAD, whereas exogenous relaxin represents a novel treatment capable of reversing established airway remodeling and AHR.
Royce
Simon G
SG
Departments of Allergy and Immunology, The Royal Children's Hospital, Parkville, Victoria, Australia.
Miao
Yu R
YR
Lee
Melissa
M
Samuel
Chrishan S
CS
Tregear
Geoffrey W
GW
Tang
Mimi L K
ML
D000818:Animals; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018893:Bronchoalveolar Lavage; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006967:Hypersensitivity / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011658:Pulmonary Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012065:Relaxin / Q000378:metabolism / Q000627:therapeutic use*
D012333:RNA, Messenger; D011994:Recombinant Proteins; D012065:Relaxin; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9