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Am J Respir Crit Care Med ; 166(5): 732-7, 2002 Sep 01.
Article in English | MEDLINE | ID: mdl-12204873

ABSTRACT

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.


Subject(s)
Airway Obstruction/immunology , Airway Obstruction/therapy , Antigens, Differentiation/pharmacology , Asthma/immunology , Asthma/therapy , Genetic Therapy/methods , Interleukin-5/genetics , Animals , Antigens , Bronchoalveolar Lavage Fluid/cytology , Disease Models, Animal , Down-Regulation , Galectin 3 , Immunoblotting , Male , Polymerase Chain Reaction , Random Allocation , Rats , Rats, Inbred BN , Reference Values , Respiratory Function Tests , Sensitivity and Specificity
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