Document Detail


Alleviation of lung inflammatory responses by adeno-associated virus 2/9 vector carrying CC10 in OVA-sensitized mice.
MedLine Citation:
PMID:  23013277     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Asthma is a chronic airway inflammatory disease characterized by eosinophilic infiltration and airway hyperresponsiveness. The over-activated Th2 and lung epithelium cells express many different cytokines, and chemokines mainly contribute to the severity of lung inflammation. Clara cell 10 kD protein (CC10) is highly expressed in airway epithelium cells and exhibits anti-inflammatory and immunomodulatory effects. Adeno-associated virus (AAV) 2/9 vector, composed of AAV2 rep and AAV9 cap genes, can efficiently and specifically target lung epithelium cells. Thus, AAV2/9 vector might carry therapeutic potential gene sequences for the treatment of asthma. This study tested whether AAV2/9 vector carrying CC10 could reduce inflammatory and asthmatic responses in OVA-induced asthmatic mouse model. The results showed that AAV2/9-CC10 vector virus significantly reduced airway hyperresponsiveness, CCL11, interleukin (IL)-4, IL-5, IL-6, IL-13, and eosinophilia in the lungs of sensitized mice. CC10 level in OVA-sensitized mice was rescued with the administration of AAV2/9-CC10 vector virus. Lung tissue remodeling, including collagen deposition and goblet cell hyperplasia, was also alleviated. However, serum levels of OVA-specific IgG1 and IgE as well as Th2 cytokine levels in OVA-stimulated splenocyte culture supernatants were at the comparable levels to the sensitized control group. The results demonstrate that AAV2/9-CC10 vector virus relieved local inflammatory and asthmatic responses in lung. Therefore, we propose that AAV2/9-CC10 vector virus guaranteed sufficient CC10 expression and had an anti-inflammatory effect in asthmatic mice. It might be applied as a novel therapeutic approach for asthma.
Authors:
Chia-Jen Wu; Li-Chen Chen; Wen-Chung Huang; Chang-Lin Chuang; Ming-Ling Kuo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-14
Journal Detail:
Title:  Human gene therapy     Volume:  24     ISSN:  1557-7422     ISO Abbreviation:  Hum. Gene Ther.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-23     Completed Date:  2013-07-05     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  9008950     Medline TA:  Hum Gene Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  48-57     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Asthma / chemically induced,  physiopathology*,  therapy*
Bronchial Hyperreactivity / therapy
Bronchoalveolar Lavage Fluid / chemistry
DNA Primers / genetics
Dependovirus
Genetic Therapy / methods*
Genetic Vectors / therapeutic use*
Immunoglobulin E / blood
Immunoglobulin G / blood
Immunohistochemistry
Interleukins / blood
Lung / pathology
Mice
NIH 3T3 Cells
Ovalbumin / toxicity
Treatment Outcome
Uteroglobin / therapeutic use*
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Immunoglobulin G; 0/Interleukins; 0/Scgb1a1 protein, mouse; 37341-29-0/Immunoglobulin E; 9006-59-1/Ovalbumin; 9060-09-7/Uteroglobin
Comments/Corrections

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