title: Inhibition of chronic airway inflammation and remodeling by galectin-3 gene therapy in a murine model.
abstract: We previously demonstrated that treatment of acute asthmatic rats with gene therapy using plasmid-encoding Galectin-3 (Gal-3) resulted in an improvement of cellular and functional respiratory parameters. The next question that we wanted to clarify was if in a chronic situation where the treated animal continues to inhale the Ag, does this procedure prevent the chronicity and the remodeling? Chronic inflammation was induced by intranasal administration of OVA over a period of 12 wk. In the treated group, the Gal-3 gene was introduced by intranasal instillation in 50 mul of plasmid-encoding Gal-3. Noninvasive airway responsiveness to methacholine was tested at different times. Cells were obtained by bronchoalveolar lavage and used for RNA extraction and cytometric studies. Eosinophils were counted in blood and bronchoalveolar lavage fluid. Real-time PCR was used to measure Gal-3 and cytokine mRNA expression in lung. Lungs were paraffined and histologic analyses were performed (H&E, periodic acid-Schiff, and Masson Trichrome stain). Our results showed that 12 wk after the first intranasal Ag instillation in chronically asthmatic mice, treatment with the Gal-3 gene led to an improvement in the eosinophil count and the normalization of hyperresponsiveness to methacholine. Concomitantly, this treatment resulted in an improvement in mucus secretion and subepithelial fibrosis in the chronically asthmatic mice, with a quantitatively measured reduction in lung collagen, a prominent feature of airway remodeling. Plasmid-encoding Gal-3 acts as a novel treatment for chronic asthma in mice producing nearly complete blockade of Ag responses with respect to eosinophil airway accumulation, airway hyperresponsiveness, and remodeling.
authors.affiliation: Immunology Department, Fundación Jiménez Díaz Capio, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: López
authors.forename: Victoria
authors.initials: V
authors.lastname: del Pozo
authors.forename: Teresa
authors.initials: T
authors.lastname: Miguel
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sastre
authors.forename: Carmen
authors.initials: C
authors.lastname: Seoane
authors.forename: Esther
authors.initials: E
authors.lastname: Civantos
authors.forename: Elena
authors.initials: E
authors.lastname: Llanes
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Baeza
authors.forename: Pilar
authors.initials: P
authors.lastname: Palomino
authors.forename: Blanca
authors.initials: B
authors.lastname: Cárdaba
authors.forename: Soledad
authors.initials: S
authors.lastname: Gallardo
authors.forename: Félix
authors.initials: F
authors.lastname: Manzarbeitia
authors.forename: José M
authors.initials: JM
authors.lastname: Zubeldia
authors.forename: Carlos
authors.initials: C
authors.lastname: Lahoz
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001249:Asthma / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016535:Bronchial Hyperreactivity / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D037502:Galectin 3 / Q000235:genetics* / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D010047:Ovalbumin / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D037502:Galectin 3; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin; D003094:Collagen