Immunologic Research

, 37:147

Flt3-ligand plasmid prevents the development of pathophysiological features of chronic asthma in a mouse model

  • Jehad H. Edwan
  • Devendra K. Agrawal
Article

Abstract

Airway inflammation and remodeling are primary characteristics of long-standing asthma. A balance between the TH1/TH2 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 TH1/TH2 cells 

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Copyright information

© Humana Press Inc 2007

Authors and Affiliations

  • Jehad H. Edwan
    • 1
    • 2
  • Devendra K. Agrawal
    • 1
    • 2
  1. 1.Department of Biomedical Sciences, Medical Microbiology & ImmunologyCreighton University School of MedicineOmaha
  2. 2.Department of Internal MedicineCreighton University School of MedicineOmaha
  3. 3.Medicine, and Medical Microbiology and ImmunologyCreighton University School of Medicine, CRISS IIOmaha

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