生物
吡咯烷二硫代氨基甲酸酯
分子生物学
报告基因
腺病毒科
基因表达
NFKB1型
遗传增强
NF-κB
基因
炎症
转录因子
免疫学
遗传学
作者
Paola Melotti,Elena Nicolis,Anna Tamanini,Rossella Rolfini,Andréa Pavirani,Giulio Cabrini
出处
期刊:Gene Therapy
[Springer Nature]
日期:2001-09-01
卷期号:8 (18): 1436-1442
被引量:71
标识
DOI:10.1038/sj.gt.3301533
摘要
Gene transfer to the respiratory tract by replication-deficient adenoviruses is limited by the induction of inflammatory and immune responses. We previously demonstrated that a E1-E3-deleted recombinant adenovirus carrying the expression cassette for the cystic fibrosis gene (Ad.CFTR) upregulates the expression of the pro-inflammatory intercellular adhesion molecule-1 (ICAM-1) both in vitro and in vivo. In the present work we suggest a role for the nuclear factor-kB (NF-kB) in Ad.CFTR-dependent up-regulation of ICAM-1 in respiratory epithelial A549 cells. Specifically, Ad.CFTR induced translocation of NF-kB into the nucleus and binding to the proximal -228/-218 NF-kB consensus sequence on the ICAM-1 promoter. Ad.CFTR also stimulated a 13-fold increase in NF-kB-dependent expression of the CAT reporter gene under the control of a region of the ICAM-1 promoter, including the proximal NF-kB consensus sequence. The Ad.CFTR-dependent increase of ICAM-1 mRNA was abolished by inhibitors of NF-kB, such as N-acetyl-L-cysteine, pyrrolidine dithiocarbamate, parthenolide and the synthetic peptide SN50. All these inhibitors abolished both Ad.CFTR-induced NF-kB DNA binding and transactivating activities. These results indicate a critical role of NF-kB in the pro-inflammatory response elicited by replication-deficient adenoviral vectors in respiratory cells.
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