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

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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.

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Authors and Affiliations

  1. Department of Biomedical Sciences, Medical Microbiology & Immunology, Creighton University School of Medicine, 68178, Omaha, NE

    Jehad H. Edwan PhD (Professor of Biomedical Sciences) & Devendra K. Agrawal

  2. Department of Internal Medicine, Creighton University School of Medicine, 68178, Omaha, NE

    Jehad H. Edwan PhD (Professor of Biomedical Sciences) & Devendra K. Agrawal

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  1. Jehad H. Edwan PhD
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  2. Devendra K. Agrawal
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Edwan, J.H., Agrawal, D.K. Flt3-ligand plasmid prevents the development of pathophysiological features of chronic asthma in a mouse model. Immunol Res 37, 147–159 (2007). https://doi.org/10.1007/BF02685896

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