title: Protection from Cigarette Smoke-Induced Lung Dysfunction and Damage by H2 Relaxin (Serelaxin).
abstract: Cigarette smoke (CS) is the major etiologic factor of chronic obstructive pulmonary disease (COPD), which is characterized by airway remodeling, lung inflammation and fibrosis, emphysema, and respiratory failure. The current therapies can improve COPD management but cannot arrest its progression and reduce mortality. Hence, there is a major interest in identifying molecules susceptible of development into new drugs to prevent or reduce CS-induced lung injury. Serelaxin (RLX), or recombinant human relaxin-2, is a promising candidate because of its anti-inflammatory and antifibrotic properties highlighted in lung disease models. Here, we used a guinea pig model of CS-induced lung inflammation, and remodeling reproducing some of the hallmarks of COPD. Animals exposed chronically to CS (8 weeks) were treated with vehicle or RLX, delivered by osmotic pumps (1 or 10 μg/day) or aerosol (10 μg/ml/day) during CS treatment. Controls were nonsmoking animals. RLX maintained airway compliance to a control-like pattern, likely because of its capability to counteract lung inflammation and bronchial remodeling. In fact, treatment of CS-exposed animals with RLX reduced the inflammatory recruitment of leukocytes, accompanied by a significant reduction of the release of proinflammatory cytokines (tumor necrosis factor α and interleukin-1β). Moreover, RLX was able to counteract the adverse bronchial remodeling and emphysema induced by CS exposure by reducing goblet cell hyperplasia, smooth muscle thickening, and fibrosis. Of note, RLX delivered by aerosol has shown a comparable efficacy to systemic administration in reducing CS-induced lung dysfunction and damage. In conclusion, RLX emerges as a new molecule to counteract CS-induced inflammatory lung diseases.
authors.affiliation: Anatomy and Histology Section and Histology and Embryology Research Unit, Department of Experimental and Clinical Medicine (A.P., G.B., S.C., D.G., D.B., S.N.), and Pharmacology Section, Department NEUROFARBA (L.L., E.M.), University of Florence, Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pini
authors.affiliation: Anatomy and Histology Section and Histology and Embryology Research Unit, Department of Experimental and Clinical Medicine (A.P., G.B., S.C., D.G., D.B., S.N.), and Pharmacology Section, Department NEUROFARBA (L.L., E.M.), University of Florence, Florence, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Boccalini
authors.affiliation: Anatomy and Histology Section and Histology and Embryology Research Unit, Department of Experimental and Clinical Medicine (A.P., G.B., S.C., D.G., D.B., S.N.), and Pharmacology Section, Department NEUROFARBA (L.L., E.M.), University of Florence, Florence, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lucarini
authors.affiliation: Anatomy and Histology Section and Histology and Embryology Research Unit, Department of Experimental and Clinical Medicine (A.P., G.B., S.C., D.G., D.B., S.N.), and Pharmacology Section, Department NEUROFARBA (L.L., E.M.), University of Florence, Florence, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Catarinicchia
authors.affiliation: Anatomy and Histology Section and Histology and Embryology Research Unit, Department of Experimental and Clinical Medicine (A.P., G.B., S.C., D.G., D.B., S.N.), and Pharmacology Section, Department NEUROFARBA (L.L., E.M.), University of Florence, Florence, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Guasti
authors.affiliation: Anatomy and Histology Section and Histology and Embryology Research Unit, Department of Experimental and Clinical Medicine (A.P., G.B., S.C., D.G., D.B., S.N.), and Pharmacology Section, Department NEUROFARBA (L.L., E.M.), University of Florence, Florence, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Masini
authors.affiliation: Anatomy and Histology Section and Histology and Embryology Research Unit, Department of Experimental and Clinical Medicine (A.P., G.B., S.C., D.G., D.B., S.N.), and Pharmacology Section, Department NEUROFARBA (L.L., E.M.), University of Florence, Florence, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Bani
authors.affiliation: Anatomy and Histology Section and Histology and Embryology Research Unit, Department of Experimental and Clinical Medicine (A.P., G.B., S.C., D.G., D.B., S.N.), and Pharmacology Section, Department NEUROFARBA (L.L., E.M.), University of Florence, Florence, Italy silvia.nistri@unifi.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nistri
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects; D000818:Animals; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D012065:Relaxin / Q000097:blood / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000737:chemistry*
chemical_list: D012906:Smoke; D012065:Relaxin