Abstract
Airway inflammation is a characteristic of many lung disorders, including asthma and chronic obstructive pulmonary disease. Using a murine model of allergen-induced asthma, we have demonstrated that adenovirus-mediated delivery of the nuclear factor-kappaB (NF-kappaB) inhibitory protein ABIN-1 to the lung epithelium results in a considerable reduction of allergen-induced eosinophil infiltration into the lungs. This is associated with an ABIN-1-induced decrease in allergen-specific immunoglobulin E levels in serum, as well as a significant reduction of eotaxin, interleukin-4, and interleukin-1beta in bronchoalveolar lavage fluid. These findings not only prove that NF-kappaB plays a critical role in the pathogenesis of allergic inflammation but also illustrate that inhibiting NF-kappaB could have therapeutic value in the treatment of asthma and potentially other chronic inflammatory lung diseases.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adenoviridae / genetics*
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Allergens / toxicity
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Animals
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Asthma / chemically induced
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Asthma / genetics
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Asthma / pathology
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Asthma / prevention & control*
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DNA-Binding Proteins / administration & dosage*
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / physiology
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Disease Models, Animal
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Female
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Gene Transfer Techniques*
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Inflammation / genetics
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Inflammation / prevention & control
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Intracellular Signaling Peptides and Proteins
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Lung / pathology*
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Mice
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Mice, Inbred BALB C
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / genetics
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Proteins / administration & dosage*
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Proteins / genetics
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Proteins / physiology
Substances
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Adaptor Proteins, Signal Transducing
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Allergens
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DNA-Binding Proteins
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IkappaBNS protein, mouse
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Intracellular Signaling Peptides and Proteins
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NF-kappa B
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Proteins
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TNIP1 protein, human
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Tnip2 protein, mouse