文本框: APPLICATION OF SINGLE-CHAIN INTERLEUKIN-12 DNA PLASMID TO TREAT AIRWAY HYPERRESPONSIVENESS IN ANIMAL MODEL OF ASTHMA
Lee Y-L, Chiang B-L
National Taiwan University Hospital, Taipei, Chinese Taipei

Objective: Allergic asthma strongly correlates with airway inflammation caused by the dysregulated production of cytokines secreted by allergen-specific type 2 T helper (Th2) cells. Interleukin (IL)-12 is a heterodimeric cytokine, which strongly promotes the differentiation of naive CD4+ T cells to the type 1 T helper (Th1) phenotype and suppresses the expression of Th2 cytokines.
Methods: In the present study, we investigated whether local transfer of the IL-12 gene to the respiratory tissues was able to modify allergic inflammation and airway hyperresponsiveness (AHR) in our disease model. To enhance in vivo delivery of IL-12 gene, we expressed the mouse single-chain IL-12 protein from a nonviral vector in which the two IL-12 subunits (p35 and p40) were linked by a 14-18 amino acid linker.
Results: One of these single-chain IL-12s containing an 18 amino acid polypeptide linker was stably expressed and had a high level of biological activity comparable to that of native IL-12 in vitro. In mice with Der p 1-induced asthma, local administration of this IL-12 fusion gene into the lungs significantly prevented the development of AHR, abrogated airway eosinophilia and inhibited type 2 cytokine production.
Conclusion: These findings indicated that local transfer of single-chain IL-12 fusion gene is effective in modulating pulmonary allergic responses and may be a convenient method for the future application for DNA vaccination.
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