Activation of nuclear factor kappaB in hepatitis C virus infection: implications for pathogenesis and hepatocarcinogenesis
| Autor: | Kenneth S.S. Chang, Yun-Fan Liaw, Dar-In Tai, Y. C. Chen, Cheng Yuan Peng, George Kuo, Yen-Ling Chuang, I-Shyan Sheen, Shao-Nan Huang, Chau-Ting Yeh, Sun-Lung Tsai |
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| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Carcinoma Hepatocellular Pyrrolidines Hepatitis C virus Apoptosis Biology medicine.disease_cause Transfection Antioxidants Cell Line chemistry.chemical_compound Pyrrolidine dithiocarbamate Thiocarbamates medicine Tumor Cells Cultured Humans Electrophoretic mobility shift assay Death domain Aged Hepatology Tumor Necrosis Factor-alpha Viral Core Proteins Liver Neoplasms NF-kappa B Hepatitis C Antibodies Middle Aged Virology Hepatitis C Immunohistochemistry chemistry Liver Cancer research RNA Viral Tumor necrosis factor alpha Female Tumor necrosis factor receptor 1 Signal transduction |
| Zdroj: | Hepatology (Baltimore, Md.). 31(3) |
| ISSN: | 0270-9139 |
| Popis: | The hepatitis C virus (HCV) core protein is a multifunctional protein. It may bind to the death domain of tumor necrosis factor receptor 1 (TNFR1) and to the cytoplasmic tail of lymphotoxin-beta receptor, implying that it may be involved in the apoptosis and anti-apoptosis signaling pathways. In vitro studies have been inconclusive regarding its ability to inhibit or enhance TNF-alpha-induced apoptosis. To address this issue, electrophoretic mobility shift assay (EMSA) and immunohistochemical studies were used to show the activation of nuclear factor kappaB (NF-kappaB) in HCV-infected liver tissues and in HCV core-transfected cells. The activation of NF-kappaB was correlated with the apoptosis assays. The results showed that NF-kappaB activation could be shown in HCV-infected livers and HCV core-transfected cells. The data of EMSA correlated with those of immunohistochemical studies, which revealed a higher frequency of NF-kappaB nuclear staining in HCV-infected than in normal livers. NF-kappaB activation conferred resistance to TNF-alpha-induced apoptosis in HCV core-transfected cells. Inhibition of NF-kappaB activation by pyrrolidine dithiocarbamate sensitized them to TNF-alpha-induced apoptosis. These findings suggest that HCV infection may cause anti-apoptosis by activation of NF-kappaB and implicate a mechanism by which HCV may evade the host's immune surveillance leading to viral persistence and possibly to hepatocarcinogenesis. |
| Databáze: | OpenAIRE |
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