期刊
JOURNAL OF IMMUNOLOGY
卷 188, 期 2, 页码 753-764出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1101652
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资金
- National Natural Science Foundation of China [81000864, 81090270, 81090273]
- National Key and Basic Research Development Program of China [2010CB529302]
- National Municipal Science and Technology Project [2009ZX09103-667, 2009ZX09301-009-RC06]
- Chinese Postdoctoral Science Foundation [20100471776]
IL-23 is a newly discovered proinflammatory cytokine that contributes to the maintenance and expansion of Th17 cells. IL-23 has recently been identified as playing a critical role in a number of chronic inflammatory diseases. However, the regulatory mechanism of IL-23 in chronic hepatitis B (CHB) remains largely unknown. The aims of this study were to detect the expression of IL-23 in CHB patients and to explore the molecular mechanism of hepatitis B virus (HBV)-induced IL-23 expression. Serum levels and hepatic expression of IL-23 were significantly upregulated in CHB patients. A positive correlation was found between IL-23 expression and the histological activity index score, HBV DNA load, and serum alanine aminotransferase and aspartate aminotransferase levels. HBx protein increased IL-23 expression in a dose-dependent manner. It also aided in the nuclear translocation of NF-kappa B, which directly bound to the promoters of IL-23 subunits p19 and p40 to facilitate their transcription. NF-kappa B inhibitors blocked the effect of HBx on IL-23 induction, and NF-kappa B subunits p65 and p50 increased the augmented IL-23 expression. Inhibition of ERK1/2 activation and transfection with ERK dominant-negative plasmid significantly blocked the HBx-induced IL-23 expression. Furthermore, PI3K and Ras-MEK-MAPK inhibitors significantly decreased the ERK1/2 activation and IL-23 expression. Thus, we report a new molecular mechanism for HBV-induced IL-23 expression, which involves the activation of the ERK/NF-kappa B pathway by HBx, leading to the transactivation of the IL-23 p19 and p40 promoters. The Journal of Immunology, 2012, 188: 753-764.
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