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Gene Therapy with Galectin-3 Inhibits Bronchial Obstruction and Inflammation in Antigen-challenged Rats through Interleukin-5 Gene Downregulation

Immunology and Pulmonology Departments, Fundación Jiménez Díaz, Madrid, Spain

Correspondence and requests for reprints should be addressed to Dr. Carlos Lahoz, Immunology Department, Fundación Jiménez Díaz, Avenue Reyes Catolicos 2, 28040 Madrid, Spain. E-mail: clahoz{at}fjd.es

The pathophysiology of asthma involves an intricate network of molecular and cellular interactions. Elevated Th2 cytokines (interleukin [IL]-5 and IL-4) associated with eosinophilic inflammation characterize allergic diseases and provide potential targets for immunomodulation. Recent evidence has demonstrated that galectin-3 induces selective downregulation of IL-5 gene expression in several cell types (eosinophils, T cell lines, and antigen specific T cells). Accordingly, we sought to elucidate whether in vivo intratracheal instillation of plasmid DNA encoding galectin-3 would inhibit an experimental asthmatic reaction in a rat model with increased eosinophils and T cells in bronchoalveolar fluid and impaired pulmonary function. We found that instillation of galectin-3 gene in these rats led to normalization of the eosinophil and T cell count in bronchoalveolar lavage fluid and that there was a strong concomitant inhibition of IL-5 mRNA in the lungs. As a consequence, galectin-3–treated rats showed recovery of pulmonary functional parameters, such as pulmonary pressure and expiratory flows. These data emphasize the potential utility of galectin-3 as a novel therapeutic approach for treatment of allergic asthma.

Key Words: gene therapy for asthma • interleukin-5 gene downregulation • galectin-3 • eosinophilic airway inflammation

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