Gene therapy with galectin-3 inhibits bronchial obstruction and inflammation in antigen-challenged rats through interleukin-5 gene downregulation.
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.
Immunology Department, Fundación Jiménez Díaz, Madrid, Spain.
Victoria
V
del Pozo
Marta
M
Rojo
Maria L
ML
Rubio
Isabel
I
Cortegano
Blanca
B
Cárdaba
Soledad
S
Gallardo
Mercedes
M
Ortega
Esther
E
Civantos
Esther
E
López
Carmen
C
Martín-Mosquero
Germán
G
Peces-Barba
Pilar
P
Palomino
Nicolas
N
González-Mangado
Carlos
C
Lahoz
D000402:Airway Obstruction / Q000276:immunology* / Q000628:therapy*; D000818:Animals; D000941:Antigens; D000943:Antigens, Differentiation / Q000494:pharmacology*; D001249:Asthma / Q000276:immunology* / Q000628:therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D015536:Down-Regulation; D037502:Galectin 3; D015316:Genetic Therapy / Q000379:methods*; D015151:Immunoblotting; D015848:Interleukin-5 / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D011897:Random Allocation; D051381:Rats; D011914:Rats, Inbred BN; D012016:Reference Values; D012129:Respiratory Function Tests; D012680:Sensitivity and Specificity
D000941:Antigens; D000943:Antigens, Differentiation; D037502:Galectin 3; D015848:Interleukin-5