Interferon α and Alcohol Augment Nuclear Regulatory Factor‐κB Activation in HepG2 Cells, and Interferon α Increases Pro‐Inflammatory Cytokine Production

Szabó, Gyöngyi; Catalano, Donna; Bellerose, Gary; Mandrekar, Pranoti

doi:10.1111/j.1530-0277.2001.tb02335.x

Cited by 10 publications

(9 citation statements)

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“…Regulation of NF-κB activation by acute and chronic alcohol has been reported in different cell types including hepatocytes, stellate cells, and a variety of immune cells (Kim et al, 2001;Mandrekar et al, 1997;Szabo and Mandrekar, 2002). In a previous study, we found that alcohol increased NF-κB nuclear levels and DNA binding in HepG2 cells and similar effects were shown by others in primary hepatocytes (Roman et al, 1999;Szabo et al, 2001). Although a broad variety of genes have κB binding sites, NF-κB activation in hepatocytes is generally linked to hepatocytes stress and survival (Dutta et al, 2006;He et al, 2010).…”

Section: Discussionsupporting

confidence: 54%

Alcohol Facilitates HCV RNA Replication via Upregulation of miR-122 Expression and Inhibition of Cyclin G1 in Human Hepatoma Cells

Hou¹,

Kodys²,

Szabó³

2011

Gastroenterology

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Background-Clinical studies demonstrate synergistic liver damage by alcohol and hepatitis C virus (HCV); however, the mechanisms by which alcohol promotes HCV infection remain obscure. The liver-specific microRNA-122 (miR-122) regulates HCV replication and expression of host genes, including Cyclin G1. Here, we hypothesized that alcohol regulates miR-122 expression and thereby modulates HCV RNA replication.

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Section: Discussionsupporting

confidence: 54%

Alcohol Facilitates HCV RNA Replication via Upregulation of miR-122 Expression and Inhibition of Cyclin G1 in Human Hepatoma Cells

Hou¹,

Kodys²,

Szabó³

2011

Gastroenterology

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“…NFκβ is a ubiquitous transcription factor that is activated by a wide variety of cytokines, mitogens, viruses, and free radicals [44]. We reported previously that alcohol increases NFκβ activation in HepG2 cells, and increased NFκβ activation was also reported in livers of patients with alcoholic hepatitis [31,45]. Similar activation of NFκβ was reported after expression of HCV core protein in hepatocytes [46••].…”

Section: Interactions Between Hcv-and Alcoholmediated Pathways In Causupporting

confidence: 52%

Pathogenic interactions between alcohol and hepatitis C

Szabó

2003

Curr Gastroenterol Rep

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Alcohol is the most commonly abused substance in the United States, and alcohol abuse leads to alcoholic liver disease, a long recognized major public health concern. The high prevalence of chronic hepatitis C virus (HCV) infection, along with the clinical observation that HCV infection is common in alcoholic patients presenting with liver disease, has directed attention to the interaction between alcohol and HCV infection. Clinical studies have identified alcohol use as an independent risk factor for progression of fibrosis in chronic HCV infection. Experimental evidence suggests additive inhibitory effects between HCV and alcohol on antiviral immune responses. In addition, specific pathways have been identified by which HCV core protein and alcohol interact to activate hepatocytes. Nonspecific inflammatory cell recruitment and proinflammatory cytokine activation have also been implicated in both alcohol- and HCV-induced liver diseases. Further investigation of these and other pathways by which alcohol and HCV interact should unravel the mechanisms that accelerate the progression of liver disease.

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“…The selected concentration of CAPE (20 g/mL) was based on our pilot experiments, which showed that CAPE at the concentrations of 20 to 30 g/mL resulted in a maximum inhibitory effect on HCV RNA expression without cytotoxic effect (trypan blue dye staining) on Huh.8 cells (data not shown). In addition, our pilot experiments showed that there was no cytotoxic effect of alcohol at the concentrations of 100 mmol/L 23 To minimize alcohol evaporation that diminishes alcohol concentration in the plates, we maintained alcoholtreated cells in the plates sealed with PARAFILM (American National Can, Greenwich, CT). Furthermore, to avoid evaporated alcohol contamination of control culture plates, alcohol-treated and control plates were maintained in separate incubators.…”

Section: Reagentsmentioning

confidence: 99%

Alcohol potentiates hepatitis C virus replicon expression

Zhang

Lai

et al. 2003

Hepatology

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H epatitis C virus (HCV) is responsible for the vast majority of cases of transfusion-associated and community-acquired non-A, non-B hepatitis 1,2 and infects an estimated 170 million people worldwide. 3 The seroprevalence of anti-HCV antibody in the United States has been estimated at 1.8%, which corresponds to approximately 4 million people. 4 HCV is the leading cause of chronic viral hepatitis in the United States, 5 and HCV-infected individuals are the major recipients of liver transplantation. HCV, first molecularly cloned in 1989, 1 is a positive-strand RNA virus of the flavivirus family with a genome size of ϳ10 kb, which encodes a number of structural (core, E1, E2, and p7) and nonstructural (NS2, NS3, NS4A, NS4B, NS5A and NS5B) proteins. 6 HCV has at least 6 distinct but related genotypes with more than 50 subtypes, and genotype 1 is the most common in the United States, Europe, and most parts of Asia. HCV typically escapes clearance by the host's immune system and leads to the establishment of a persistent infection in approximately 70% of infected individuals. 7 The consequences of a subset of patients with chronic HCV infection are cirrhosis, liver failure, and hepatocellular carcinoma. 8,9 Treatment of HCV with interferon alfa (IFN-␣) and ribavirin is associated with a sustained response rate of less than 50%. 7,10,11 These limited therapeutic efficacies and the absence of an effective HCV vaccine underscore the importance of research on factors that enhance HCV infection and compromise IFN-␣-based therapy.Alcohol is the most commonly used and abused drug in the United States. Alcohol abuse significantly affects morbidity and mortality from infectious diseases. 12 Alcohol consumption accelerates liver damage, diminishes therapeutic response to IFN-␣, and increases the rate of hepatocellular carcinoma in patients with chronic HCV

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Interferon α and Alcohol Augment Nuclear Regulatory Factor‐κB Activation in HepG2 Cells, and Interferon α Increases Pro‐Inflammatory Cytokine Production

Cited by 10 publications

References 51 publications

Alcohol Facilitates HCV RNA Replication via Upregulation of miR-122 Expression and Inhibition of Cyclin G1 in Human Hepatoma Cells

Alcohol Facilitates HCV RNA Replication via Upregulation of miR-122 Expression and Inhibition of Cyclin G1 in Human Hepatoma Cells

Pathogenic interactions between alcohol and hepatitis C

Alcohol potentiates hepatitis C virus replicon expression

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