Hepatitis B virus X protein transactivates the inducible nitric oxide synthase promoter

被引:28
作者
Amaro, MJ
Bartolomé, J
Carreño, V
机构
[1] Fdn Jimenez Diaz, Dept Hepatol, Madrid 228040, Spain
[2] Fdn Estudio Hepatitis Virales, Madrid, Spain
关键词
D O I
10.1002/hep.510290337
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The capability of hepatitis B virus (HBV) to increase the transcription of the human hepatic inducible nitric oxide synthase (iNOS) by transactivating its promoter has been studied. We have observed by reverse-transcription polymerase chain reaction (RT-PCR) that although the mRNA for the iNOS was almost undetectable in the human hepatoblastoma cell line, HepG2, it was constitutively expressed in the 2.2.15 cell line (a derivative of the HepG2 that produces complete HBV particles). Transfection of HepG2 and 2.2.15 cells with the pliNOS-CAT plasmid (containing a 1.1-kb fragment of the iNOS promoter) resulted in an increase in chloramphenicol acetyl transferase (CAT) activity in 2.2.15 cells. Similar results were observed when HepG2 and Chang liver cell lines were cotransfected with the pliNOS-CAT plasmid and the complete HBV genome. It was shown that pX was responsible for the transactivation by cotransfection of NepG2 cells with the pliNOS-CAT and plasmids expressing the HBV-encoded pX protein, core antigen, and e antigen. Cotransfection of HepG2 cells with the pX expression plasmids and a series of deletion mutants of the 1.1-kb iNOS promoter fragments established that transactivation by pX depends on the presence of at least one nuclear factor-kappa B (NF-kappa B) binding site. This was further confirmed by cotransfecting cells with a plasmid expressing the NF-kappa B inhibitor, I kappa B.
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页码:915 / 923
页数:9
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