Treatment with Flt3 ligand plasmid reverses allergic airway inflammation in ovalbumin-sensitized and -challenged mice

Jehad H. Edwan, James E Talmadge, Devendra K. Agrawal

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

We have previously reported that fms-like tyrosine kinase 3 ligand (Flt3-L) prevents and reverses established allergic airway inflammation in an ovalbumin (OVA) induced mouse model of asthma. In this study, we investigated the effect of pUMVC3-hFLex, a plasmid, mammalian expression vector for the secretion of Flt3-L on the same mouse model as well as the duration of the effect of the treatment. Allergic airway inflammation to OVA was established in BALB/c mice. OVA-sensitized mice received three intramuscular (i.m.) injections of 200 μg pUMVC3-hFLex over 10 days. The response to pUMVC3-hFLex therapy was assessed based on airway hyperresponsiveness (AHR) to methacholine and inflammation, measured as serum cytokine and immunoglobulins (Ig) levels, and the total and differential cells in bronchoalveolar lavage fluid (BALF). pUMVC3-hFLex treatment completely reversed established AHR (P<0.01) and this effect lasted for at least 24 days after the last treatment injection (P<0.001). pUMVC3-hFLex treatment significantly increased BALF interferon-gamma (IFN-γ) (P<0.01), serum interleukin (IL)-10 (P<0.01) and anti-OVA IgG2a levels (P<0.01). In contrast, serum IL-4 and IgE levels were significantly reduced (P<0.05). Total BALF cellularity, eosinophiles counts and BALF IL-5 levels were also reduced (P<0.01). pUMVC3-hFLex treatment can reverse established experimental asthma and might provide a novel approach for treating asthma.

Original languageEnglish (US)
Pages (from-to)345-357
Number of pages13
JournalInternational Immunopharmacology
Volume5
Issue number2
DOIs
StatePublished - Feb 1 2005

Fingerprint

Ovalbumin
Plasmids
Bronchoalveolar Lavage Fluid
Inflammation
Asthma
Therapeutics
Serum
Methacholine Chloride
Intramuscular Injections
Interleukin-5
Eosinophils
Interleukin-4
Interleukin-10
Immunoglobulin E
Interferon-gamma
flt3 ligand protein
Immunoglobulins
Cytokines
Injections

Keywords

  • Allergy
  • Asthma
  • Flt3-L
  • OVA mouse model
  • TH1/TH2 cells
  • pUMVC3-hFLex

ASJC Scopus subject areas

  • Immunology
  • Pharmacology

Cite this

Treatment with Flt3 ligand plasmid reverses allergic airway inflammation in ovalbumin-sensitized and -challenged mice. / Edwan, Jehad H.; Talmadge, James E; Agrawal, Devendra K.

In: International Immunopharmacology, Vol. 5, No. 2, 01.02.2005, p. 345-357.

Research output: Contribution to journalArticle

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