TY - JOUR
T1 - Treatment with Flt3 ligand plasmid reverses allergic airway inflammation in ovalbumin-sensitized and -challenged mice
AU - Edwan, Jehad H.
AU - Talmadge, James E.
AU - Agrawal, Devendra K.
PY - 2005/2
Y1 - 2005/2
N2 - 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.
AB - 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.
KW - Allergy
KW - Asthma
KW - Flt3-L
KW - OVA mouse model
KW - TH1/TH2 cells
KW - pUMVC3-hFLex
UR - http://www.scopus.com/inward/record.url?scp=12344298548&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12344298548&partnerID=8YFLogxK
U2 - 10.1016/j.intimp.2004.10.002
DO - 10.1016/j.intimp.2004.10.002
M3 - Article
C2 - 15652764
AN - SCOPUS:12344298548
VL - 5
SP - 345
EP - 357
JO - International Immunopharmacology
JF - International Immunopharmacology
SN - 1567-5769
IS - 2
ER -