Human hepatocytes infected by hepatitis B virus (HBV) produce the proinflammatory cytokine, tumor necrosis factor alpha (TNF-alpha). In this study, we explored the mechanism of induction of TNF-alpha synthesis by HBV. We found that the stable HBV-transfected hepatoma cell line, 2.2.15, expressed high-molecular-weight (HMW) TNF-alpha mRNAs, which were absent in the parent HepG2 cells. Treatment of 2.2.15 cells with interferon alfa (IFN-alpha) and/or interleukin-1 beta (IL-1 beta) reduced both viral gene transcription and TNF-alpha mRNA expression. Transient or stable transfection of hepatocyte-derived cell lines with HBV X protein (HBx) expression vectors induced the production of biologically active TNF-alpha. In these cells, the HBx-induced TNF-alpha was detected both as cell-associated and soluble forms. Luciferase gene-expression assays showed that the TNF-alpha gene promoter contained target sequences for HBx trans-activation within the proximal region of the promoter. These results indicate that the hepatocyte TNF-alpha synthesis induced by HBV is transcriptionally up-regulated by HBx. Thus, HBx may have a role in the induction of the intrahepatic inflammatory processes that take place during acute and chronic hepatitis B.

The hepatitis B virus X protein up-regulates tumor necrosis factor alpha gene expression in hepatocytes / E., Lara Pezzi; P. L., Majano; M., Gomez Gonzalo; C., Garcia Monzon; R., Moreno Otero; Levrero, Massimo; M., Lopez Cabrera. - In: HEPATOLOGY. - ISSN 0270-9139. - 28:4 I(1998), pp. 1013-1021. [10.1002/hep.510280416]

The hepatitis B virus X protein up-regulates tumor necrosis factor alpha gene expression in hepatocytes

LEVRERO, Massimo;
1998

Abstract

Human hepatocytes infected by hepatitis B virus (HBV) produce the proinflammatory cytokine, tumor necrosis factor alpha (TNF-alpha). In this study, we explored the mechanism of induction of TNF-alpha synthesis by HBV. We found that the stable HBV-transfected hepatoma cell line, 2.2.15, expressed high-molecular-weight (HMW) TNF-alpha mRNAs, which were absent in the parent HepG2 cells. Treatment of 2.2.15 cells with interferon alfa (IFN-alpha) and/or interleukin-1 beta (IL-1 beta) reduced both viral gene transcription and TNF-alpha mRNA expression. Transient or stable transfection of hepatocyte-derived cell lines with HBV X protein (HBx) expression vectors induced the production of biologically active TNF-alpha. In these cells, the HBx-induced TNF-alpha was detected both as cell-associated and soluble forms. Luciferase gene-expression assays showed that the TNF-alpha gene promoter contained target sequences for HBx trans-activation within the proximal region of the promoter. These results indicate that the hepatocyte TNF-alpha synthesis induced by HBV is transcriptionally up-regulated by HBx. Thus, HBx may have a role in the induction of the intrahepatic inflammatory processes that take place during acute and chronic hepatitis B.
1998
01 Pubblicazione su rivista::01a Articolo in rivista
The hepatitis B virus X protein up-regulates tumor necrosis factor alpha gene expression in hepatocytes / E., Lara Pezzi; P. L., Majano; M., Gomez Gonzalo; C., Garcia Monzon; R., Moreno Otero; Levrero, Massimo; M., Lopez Cabrera. - In: HEPATOLOGY. - ISSN 0270-9139. - 28:4 I(1998), pp. 1013-1021. [10.1002/hep.510280416]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/438345
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