期刊
VIROLOGY
卷 444, 期 1-2, 页码 317-328出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2013.06.028
关键词
Hepatitis B virus chronic infection; Interleukin-8; IL-8 promoter; Transcription factors; Hepatitis B X viral regulatory protein; Signal pathways; Chromatin immunoprecipitation; Chromatin modifying enzymes; IL-8 siRNA; Interferon-alpha
类别
资金
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG 12022]
High levels of serum interleukin-8 (IL-8) have been detected in chronic hepatitis B (CHB) patients during episodes of hepatitis flares. We investigated whether hepatitis B virus (HBV) may directly induce IL-8 production and whether IL-8 may antagonize interferon-alpha (IFN-alpha) antiviral activity against HBV. We showed that CHB patients had significantly higher IL-8 levels both in serum and in liver tissue than controls. In HBV-replicating HepG2 cells, IL-8 transcription was significantly activated. AP-1, C/EBP and NF-kB transcription factors were concurrently necessary for maximum IL-8 induction. Moreover, HBx viral protein was recruited onto the IL-8 promoter and this was paralleled by IL8-bound histone hyperacetylation and by active recruitment of transcriptional coactivators. Inhibition of IL-8 increases the antiviral activity of IFN-alpha against HBV. Our results indicate that HBV activates IL-8 gene expression by targeting the epigenetic regulation of the IL-8 promoter and that IL-8 may contribute to reduce HBV sensitivity to IFN-alpha. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
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