Flt3-ligand plasmid prevents the development of pathophysiological features of chronic asthma in a mouse model
Cite this article as: Edwan, J.H. & Agrawal, D.K. Immunol Res (2007) 37: 147. doi:10.1007/BF02685896 Abstract
Airway inflammation and remodeling are primary characteristics of long-standing asthma. A balance between the T
H1/T H2 cytokines regulates the accumulation and activation of inflammatory cells, including mast cells and eosinophils. Recently, we demonstrated that pUMVC3-hFLex, an active plasmid, mammalian expression vector for the secretion of Flt3-L, reversed established airway hyperresponsiveness (AHR) in a murine model of acute allergic airway inflammation. The present experiments were undertaken to examine the effect of pUMVC3-hFLex in a chronic model of allergic airway inflammation that was established in Balb/c mice by sensitization and challenge with ovalbumin (OVA). pUMVC3-hFLex or the control plasmid, pUMVC3, were administered by injection into the muscle interior tibialis. Treatment with pUMVC3-hFLex completely reversed established AHR ( p<0.05), and this effect continued even after several exposures to the allergen ( p<0.05). pUMVC3-hFLex treatment prevented the development of goblet cell hyperplasia and subepithelial fibrosis, and significantly reduced serum levels of IL-4 and IL-5, and increased serum IL-10 levels ( p<0.05) with no effect on serum IL-13. Serum IgE or serum total and anti-OVA IgG1 and IgG2a levels did not change. Total BALF cellularity and BALF IL-5 levels were reduced ( p<0.05), but there was no significant effect on BALF IL-10 and IL-13. These results suggest that pUMVC3-hFLex treatment can prevent the development of airway remodeling and maintain airway protection in chronic experimental asthma model, and might provide a novel approach for treating chronic asthma. Key Words Allergy Asthma Flt3-L Mouse model of asthma pUMVC3-hFLex plasmid T H1/T H2 cells References
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