RGD Reference Report - Suppression of furin by interferon-γ and the impact on hepatitis B virus antigen biosynthesis in human hepatocytes.

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Suppression of furin by interferon-γ and the impact on hepatitis B virus antigen biosynthesis in human hepatocytes.
Authors:	Wu, Jia-Feng Hsu, Hong-Yuan Ni, Yen-Hsuan Chen, Huey-Ling Wu, Tzee-Chung Chang, Mei-Hwei
Citation:	Wu JF, etal., Am J Pathol. 2012 Jul;181(1):19-25. doi: 10.1016/j.ajpath.2012.03.036. Epub 2012 May 24.
RGD ID:	36947881
Pubmed:	PMID:22634051 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.ajpath.2012.03.036 (Journal Full-text)
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.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
PDCD1	Human	Chronic Hepatitis B		IEP		mRNA:increased expression:liver parenchyma (human)	RGD

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Genes (Homo sapiens)

PDCD1 (programmed cell death 1)

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Gene	Pdcd1	programmed cell death 1	Mus musculus
Gene	Pdcd1	programmed cell death 1	Rattus norvegicus

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Suppression of furin by interferon-γ and the impact on hepatitis B virus antigen biosynthesis in human hepatocytes.