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Relaxin Reverses Airway Remodeling and Airway Dysfunction in Allergic Airways Disease

Department of Allergy and Immune Disorders (S.G.R., Y.R.M., M.L., M.L.K.T.), Murdoch Children’s Research Institute, and Department of Allergy and Immunology (M.L.K.T.), The Royal Children’s Hospital, Parkville, Victoria 3052, Australia; and Howard Florey Institute (C.S.S., G.W.T.), and Department of Biochemistry and Molecular Biology (C.S.S., G.W.T.), The University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia

Address all correspondence and requests for reprints to: Associate Professor Mimi L. K. Tang, M.D., Ph.D., Departments of Allergy and Immunology, The Royal Children’s Hospital, Flemington Road, Parkville, Victoria 3052, Australia. E-mail: mimi.tang{at}rch.org.au.

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.