RRC ID 2026
Author Ogawa H, Nishimura N, Nishioka Y, Azuma M, Yanagawa H, Sone S.
Title Adenoviral interleukin-12 gene transduction into human bronchial epithelial cells: up-regulation of pro-inflammatory cytokines and its prevention by corticosteroids.
Journal Clin. Exp. Allergy
Abstract BACKGROUND:One of the potential effects of IL-12 is to restore Th1/Th2 balance. Therefore, we investigated the possibility of developing a system for local delivery of IL-12 into the airways by examining protein expression in a human bronchial epithelial cell line (BEAS-2B) after adenoviral IL-12 gene transduction. The effects of dexamethasone on the gene-modified cells were also examined.
METHODS:Adenoviral vectors AxCAegfp and Ax1CIhp40ip35 were used to transduce enhanced green fluorescence protein and IL-12 genes, respectively, into BEAS-2B cells. Wild-type and IL-12 gene-transduced BEAS-2B cells were then incubated with or without dexamethasone, and concentrations of IL-12, IFN-gamma, IL-6, IL-8, granulocyte macrophage-colony stimulating factor and chemokines (TARC and RANTES) in the supernatant were measured by ELISA. IL-12 receptor expression was analysed by flow cytometry and RT-PCR.
RESULTS:The efficiency of transgene expression in BEAS-2B cells at a multiplicity of infection of 30 was approximately 80%. Gene-modified BEAS-2B cells produced biologically active IL-12, regardless of dexamethasone treatment. While IL-12 gene transduction led to increased production of IL-6 and IL-8 by BEAS-2B cells, expressions of these proteins were suppressed by dexamethasone. Addition of exogenous IL-12 failed to augment BEAS-2B cell IL-6 and IL-8 production, and IL-12 receptor expression by BEAS-2B cells was not detected.
CONCLUSIONS:Our findings suggest that adenoviral IL-12 gene transduction may be effective in inducing IL-12 expression in the airways, and could be a potential approach in the management of bronchial asthma.
Volume 33(7)
Pages 921-9
Published 2003-7
PII 1702
PMID 12859448
MeSH Adenoviridae Bronchi Cell Line Dexamethasone / pharmacology* Enzyme-Linked Immunosorbent Assay Flow Cytometry Genetic Vectors Glucocorticoids / pharmacology* Humans Interleukin-12 / genetics* Interleukin-6 / metabolism Interleukin-8 / metabolism RNA / metabolism Respiratory Mucosa Reverse Transcriptase Polymerase Chain Reaction Transduction, Genetic Up-Regulation
IF 5.158
Times Cited 7
DNA material Ax1 CI hp40ip35 (RDB01739)