Hepatitis B virus X protein transactivates human interleukin-8 gene through acting on nuclear factor kB and CCAAT/enhancer-binding protein-like cis-elements.
Interleukin-8 (IL-8) is a newly described leukocyte chemotactic and activating cytokine that belongs to the novel family of inflammatory cytokines whose genes locate on human chromosome 4, q12-21 region. The production of IL-8 is usually not constitutive and can be induced rapidly and abundantly in different cell types by a variety of stimuli such as lipopolysaccharide, interleukin-1, tumor necrosis factor-alpha as well as a tumor promotor phorbol myristate acetate. We report here that in addition to these stimuli the IL-8 gene can also be induced by the protein X of the hepatitis B virus (HBV-X) as evidenced by the enhanced IL-8 mRNA expression and IL-8 production observed in HBV-X-transfected cells. Furthermore, using several deletion mutants of the 5'-flanking regulatory region of the human IL-8 gene linked to the chloramphenicol acetyl transferase gene as a reporter, we have established here that both nuclear factor kB and CCAAT/enhancer-binding protein-like cis-elements located at -94 to -71 base pairs of IL-8 gene are essential and sufficient for the induction of the IL-8 gene by HBV-X. The same elements have been identified recently by us to be interleukin-1-, tumor necrosis factor-alpha-, and phorbol myristate acetate-responsive elements on the IL-8 gene. This suggests the existence of a common pathway for these inflammatory cytokines and HBV-X to activate the IL-8 gene. These observations might be relevant to the pathogenesis of inflammation in viral hepatitis.
Mahé
Y
Y
Department of Pharmacology, Kanazawa University, Ishikawa, Japan.
Mukaida
N
N
Kuno
K
K
Akiyama
M
M
Ikeda
N
N
Matsushima
K
K
Murakami
S
S
D001483:Base Sequence; D015152:Blotting, Northern; D022762:CCAAT-Enhancer-Binding Proteins; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006511:Hepatitis B Antigens / Q000502:physiology; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D016209:Interleukin-8 / Q000235:genetics*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D009841:Oligonucleotides / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D054334:Viral Regulatory and Accessory Proteins
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D006511:Hepatitis B Antigens; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D009687:Nuclear Proteins; D009841:Oligonucleotides; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D013755:Tetradecanoylphorbol Acetate