|Title:||Suppression of furin by interferon-γ and the impact on hepatitis B virus antigen biosynthesis in human hepatocytes||Authors:||JIA-FENG WU
|Issue Date:||2012||Journal Volume:||181||Journal Issue:||1||Start page/Pages:||19-25||Source:||American Journal of Pathology||Abstract:||
The roles of furin and intrahepatic cytokines in chronic heptatitis B virus (HBV) infection remain largely unknown. Here, we examined the relations between furin, IL-10, IL-12β, interferon (IFN)-γ, programed death (PD)-1, programed death ligand (PD-L)1, and the suppression of hepatitis B e antigen (HBeAg) and surface antigen (HBsAg) biosynthesis. Liver biopsies were performed on 20 chronically HBV-infected (15 HBeAg-positive and 5 HBeAg-negative) patients to assess liver inflammation/fibrosis, and mRNA levels of furin, IL-10, IL-12β, IFN-γ, PD-1, and PD-L1 were assessed by quantitative real-time PCR. IFN-γ mRNA abundance was associated with lower furin mRNA levels and higher PD-1 and PD-L1 mRNA levels in liver tissue from HBeAg-positive patients. IL-10 and IL-12β mRNA levels positively correlated with IFN-γ expression levels (P < 0.05). PD-L1 and furin mRNA levels were further assessed in IFN-γ-stimulated hepatoma cell lines with (HepG2.2.15 cells) and without (HepG2 and Huh7 cells) HBV replication. IFN-γ enhanced PD-L1 expression in hepatoma cells. In HepG2.2.15 cells, IFN-γ further suppressed furin and HBeAg expression. Furin inhibition and knockdown in HepG2.2.15 cells also down-regulated HBeAg and HBsAg biosynthesis. These data suggest that IFN-γ modulates the inflammatory response to avoid excessive hepatocyte damage through the enhancement of PD-1/PD-L1 expression, whereas furin suppression may contribute to a reduction in HBeAg/HBsAg biosynthesis. Copyright ? 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
|ISSN:||0002-9440||DOI:||10.1016/j.ajpath.2012.03.036||SDG/Keyword:||furin; gamma interferon; hepatitis B surface antigen; hepatitis B(e) antigen; interleukin 10; interleukin 12p40; messenger RNA; programmed death 1 ligand 1; programmed death 1 receptor; article; clinical article; controlled study; hepatitis B; human; liver fibrosis; priority journal; protein function; protein protein interaction; quantitative analysis; real time polymerase chain reaction; Adolescent; Antigens, CD274; Carcinoma, Hepatocellular; Child; Child, Preschool; Cytokines; Down-Regulation; Female; Furin; Gene Knockdown Techniques; Hepatitis B Antigens; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B, Chronic; Hepatocytes; Humans; Interferon-gamma; Liver; Liver Neoplasms; Male; Programmed Cell Death 1 Receptor; RNA, Messenger; Tumor Cells, Cultured; Up-Regulation; Young Adult
|Appears in Collections:||醫學系|
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