Linked Life Data

18023072

Source:http://linkedlifedata.com/resource/pubmed/id/18023072

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-12-24
pubmed:abstractText
Recently, we have developed a model of airway inflammation in a CFTR knockout mouse utilizing Aspergillus fumigatus crude protein extract (Af-cpe) to mimic allergic bronchopulmonary aspergillosis (ABPA) 1, an unusual IgE-mediated hypersensitivity syndrome seen in up to 15% of cystic fibrosis (CF) patients and rarely elsewhere. We hypothesized that replacement of CFTR via targeted gene delivery to airway epithelium would correct aberrant epithelial cytokine signaling and ameliorate the ABPA phenotype in CFTR-deficient (CFTR 489X - /-, FABP-hCFTR + / +) mice. CFTR knockout mice underwent intra-tracheal (IT) delivery of recombinant adeno-associated virus serotype 5 (rAAV5Delta-264CFTR) or rAAV5-GFP at 2.58 x 10(12) viral genomes/mouse. All mice were then sensitized with two serial injections (200 microg) of crude Af antigen via the intra-peritoneal (IP) route. Untreated mice were sensitized without virus exposure. Challenges were performed 2 weeks after final sensitization, using a 0.25% solution containing Aspergillus fumigatus crude protein extract delivered by inhalation on three consecutive days. The rAAV5Delta-264CFTR-treated mice had lower total serum IgE levels (172513 ng/ml +/- 1312) than rAAV5-GFP controls (26 892 ng/ml +/- 3715) (p = 0.037) and non-treated, sensitized controls (24 816 +/- 4219 ng/ml). Serum IgG1 levels also were lower in mice receiving the CFTR vector. Interestingly, splenocytes from rAAV5Delta-264CFTR-treated mice secreted less IL-13, INFg, TNFa, RANTES and GM-CSF after ConA stimulation. Gene therapy with rAAV5Delta-264CFTR attenuated the hyper-IgE response in this reproducible CF mouse model of ABPA, with systemic effects also evident in the cytokine response of stimulated splenocytes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1099-498X
pubmed:author
pubmed:copyrightInfo
(c) 2007 John Wiley & Sons, Ltd.
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
51-60
pubmed:meshHeading
pubmed-meshheading:18023072-Animals, pubmed-meshheading:18023072-Aspergillosis, Allergic Bronchopulmonary, pubmed-meshheading:18023072-Aspergillus fumigatus, pubmed-meshheading:18023072-Cell Proliferation, pubmed-meshheading:18023072-Complex Mixtures, pubmed-meshheading:18023072-Concanavalin A, pubmed-meshheading:18023072-Cystic Fibrosis Transmembrane Conductance Regulator, pubmed-meshheading:18023072-Cytokines, pubmed-meshheading:18023072-Dependovirus, pubmed-meshheading:18023072-Disease Models, Animal, pubmed-meshheading:18023072-Fluorescein-5-isothiocyanate, pubmed-meshheading:18023072-Gene Expression Regulation, pubmed-meshheading:18023072-Gene Therapy, pubmed-meshheading:18023072-Green Fluorescent Proteins, pubmed-meshheading:18023072-Humans, pubmed-meshheading:18023072-Immunoglobulin E, pubmed-meshheading:18023072-Immunologic Factors, pubmed-meshheading:18023072-Mice, pubmed-meshheading:18023072-Mice, Inbred CFTR, pubmed-meshheading:18023072-Mutant Proteins, pubmed-meshheading:18023072-Mutation, pubmed-meshheading:18023072-Spleen, pubmed-meshheading:18023072-Transduction, Genetic, pubmed-meshheading:18023072-Transgenes
pubmed:year
2008
pubmed:articleTitle
Partial correction of the CFTR-dependent ABPA mouse model with recombinant adeno-associated virus gene transfer of truncated CFTR gene.
pubmed:affiliation
Department of Pediatrics and Powell Gene Therapy Center, College of Medicine, University of Florida, Gainesville, FL, USA.
pubmed:publicationType
Journal Article