Adenoviral gene transfer of the NF-kappa B inhibitory protein ABIN-1 decreases allergic airway inflammation in a murine asthma model.
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.
El Bakkouri
Karim
K
Unit of Molecular Signal Transduction in Inflammation, Department of Molecular Biomedical Research, Ghent University-VIB, B-9052 Ghent, Belgium.
Wullaert
Andy
A
Haegman
Mira
M
Heyninck
Karen
K
Beyaert
Rudi
R
D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae / Q000235:genetics*; D000485:Allergens / Q000633:toxicity; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D004268:DNA-Binding Proteins / Q000008:administration & dosage* / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D007249:Inflammation / Q000235:genetics / Q000517:prevention & control; D047908:Intracellular Signaling Peptides and Proteins; D008168:Lung / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics; D011506:Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D000485:Allergens; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D011506:Proteins; C454819:Nfkbid protein, mouse; C117046:TNIP1 protein, human; C503281:Tnip2 protein, mouse