Flt3-ligand plasmid prevents the development of pathophysiological features of chronic asthma in a mouse model.
Airway inflammation and remodeling are primary characteristics of long-standing asthma. A balance between the T(H)1/T(H)2 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.
Edwan
Jehad H
JH
Department of Biomedical Sciences, Medical Microbiology & Immunology, Creighton University School of Medicine, Omaha, NE 68178, USA.
Agrawal
Devendra K
DK
D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005260:Female; D020397:Goblet Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D007167:Immunotherapy / Q000379:methods; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics / Q000276:immunology
D016207:Cytokines; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D008565:Membrane Proteins; C084881:flt3 ligand protein; D007073:Immunoglobulin E; D010047:Ovalbumin; D003094:Collagen
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