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ABSTRACT:
PROVIDER: PRJNA168237 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE38147: Gene expression profiling of primary human hepatocytes treated with IFN-alpha or IFN-gamma GSE38597: Gene expression profiling of 6 acute hepatitis C patients Refer to individual Series
2012-06-08 | E-GEOD-38598 | biostudies-arrayexpress
Project description:Approximately 50% of patients with chronic hepatitis C (CHC) have a sustained virologic response (SVR) to treatment with pegylated interferon (pegINF)-α and ribavirin. Non-response to treatment is associated with constitutively increased expression of IFN-stimulated genes (ISGs) in the liver. Treatment of patients with acute hepatitis C (AHC) is more effective, with SVR rates >90%. We investigated mechanisms of the different responses of patients with CHC and AHC to pegIFN-α therapy. We analyzed IFN signaling and ISG expression in liver samples from patients with acute hepatitis C (AHC), patients with chronic hepatitis (CHC), and individuals without hepatitis C (controls) using microarray, immunohistochemical, and protein analyses. Findings were compared with those from primary human hepatocytes stimulated with IFN-α or IFN-γ, as reference sets. Expression levels of 100s of genes, primarily those regulated by IFN-γ, were altered in liver samples from patients with AHC compared with controls. Expression of IFN-γ–stimulated genes was induced in liver samples from patients with AHC, whereas expression of IFN-α–stimulated genes was induced in samples from patients with CHC. In an expression analysis of negative regulators of IFN-α signaling, we did not observe differences in expression of SOCS1 or SOCS3 between liver samples from patients with AHC and those with CHC. However, USP18 (another negative regulator of IFN-α signaling), was upregulated in liver samples of patients with CHC that did not respond to therapy, but not in AHC. In conclusion, differences in expression of ISGs might account for the greater response of patients with AHC, compared to those with CHC, to treatment with pegINF-α and ribavirin. Specifically, USP18 is upregulated in liver samples of patients with CHC that do not respond to therapy, but not in patients with AHC. (Interferon-γ Stimulated Genes, but not USP18, are Expressed in Livers of Patients with Acute Hepatitis C; Dill MT, Makowska Z et al, Gastroenterology 2012 (in press)) Primary human hepatocytes from 2 donors were analyzed. From each donor there are 5 samples: untreated cells, cells treated with interferon alpha (1000 IU/ml) for 6 and 24 hours and cells treated with interferon gamma (1000 IU/ml) for 6 and 24 hours.
2012-06-08 | E-GEOD-38147 | biostudies-arrayexpress
Project description:Approximately 50% of patients with chronic hepatitis C (CHC) have a sustained virologic response (SVR) to treatment with pegylated interferon (pegINF)-α and ribavirin. Non-response to treatment is associated with constitutively increased expression of IFN-stimulated genes (ISGs) in the liver. Treatment of patients with acute hepatitis C (AHC) is more effective, with SVR rates >90%. We investigated mechanisms of the different responses of patients with CHC and AHC to pegIFN-α therapy. We analyzed IFN signaling and ISG expression in liver samples from patients with acute hepatitis C (AHC), patients with chronic hepatitis (CHC), and individuals without hepatitis C (controls) using microarray, immunohistochemical, and protein analyses. Findings were compared with those from primary human hepatocytes stimulated with IFN-α or IFN-γ, as reference sets. Expression levels of 100s of genes, primarily those regulated by IFN-γ, were altered in liver samples from patients with AHC compared with controls. Expression of IFN-γ–stimulated genes was induced in liver samples from patients with AHC, whereas expression of IFN-α–stimulated genes was induced in samples from patients with CHC. In an expression analysis of negative regulators of IFN-α signaling, we did not observe differences in expression of SOCS1 or SOCS3 between liver samples from patients with AHC and those with CHC. However, USP18 (another negative regulator of IFN-α signaling), was upregulated in liver samples of patients with CHC that did not respond to therapy, but not in AHC. In conclusion, differences in expression of ISGs might account for the greater response of patients with AHC, compared to those with CHC, to treatment with pegINF-α and ribavirin. Specifically, USP18 is upregulated in liver samples of patients with CHC that do not respond to therapy, but not in patients with AHC. (Interferon-γ Stimulated Genes, but not USP18, are Expressed in Livers of Patients with Acute Hepatitis C; Dill MT, Makowska Z et al, Gastroenterology 2012 (in press))
2012-06-09 | GSE38597 | GEO
Project description:Approximately 50% of patients with chronic hepatitis C (CHC) have a sustained virologic response (SVR) to treatment with pegylated interferon (pegINF)-α and ribavirin. Non-response to treatment is associated with constitutively increased expression of IFN-stimulated genes (ISGs) in the liver. Treatment of patients with acute hepatitis C (AHC) is more effective, with SVR rates >90%. We investigated mechanisms of the different responses of patients with CHC and AHC to pegIFN-α therapy. We analyzed IFN signaling and ISG expression in liver samples from patients with acute hepatitis C (AHC), patients with chronic hepatitis (CHC), and individuals without hepatitis C (controls) using microarray, immunohistochemical, and protein analyses. Findings were compared with those from primary human hepatocytes stimulated with IFN-α or IFN-γ, as reference sets. Expression levels of 100s of genes, primarily those regulated by IFN-γ, were altered in liver samples from patients with AHC compared with controls. Expression of IFN-γ–stimulated genes was induced in liver samples from patients with AHC, whereas expression of IFN-α–stimulated genes was induced in samples from patients with CHC. In an expression analysis of negative regulators of IFN-α signaling, we did not observe differences in expression of SOCS1 or SOCS3 between liver samples from patients with AHC and those with CHC. However, USP18 (another negative regulator of IFN-α signaling), was upregulated in liver samples of patients with CHC that did not respond to therapy, but not in AHC. In conclusion, differences in expression of ISGs might account for the greater response of patients with AHC, compared to those with CHC, to treatment with pegINF-α and ribavirin. Specifically, USP18 is upregulated in liver samples of patients with CHC that do not respond to therapy, but not in patients with AHC. (Interferon-γ Stimulated Genes, but not USP18, are Expressed in Livers of Patients with Acute Hepatitis C; Dill MT, Makowska Z et al, Gastroenterology 2012 (in press))
2012-06-09 | GSE38147 | GEO
Project description:Hepatitis B virus (HBV) infection is a risk of developing fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma. Although HBV elimination requires complete elimination of covalently closed circular DNA (cccDNA), its treatment has not been established. Interferon (IFN) -γ, a type ⅠⅠ IFN, is produced by intrahepatic cytotoxic T lymphocytes and has the noncytolytic antiviral potential. However, the mechanism by which IFN-γ regulates HBV infection in hepatocytes has not been fully elucidated. In this study, to replicate the HBV infection and monitor the amount of cccDNA, we developed an in vitro HBV infection assay system with primary hepatocytes and examined the molecules and signaling pathways. IFN-γ suppressed both HBV propagation and transcription to the same extent as IFN-α. RNA microarray analysis revealed that IFN-γ stimulation induced not only IFN-γ but also IFN-α signaling activation and regulated HBV cccDNA. Moreover, the HBV production was reduced by IFN-γ through JAK-STAT signaling and interferon stimulated genes such as OAS2 and APOBEC3G. Taken together, these results demonstrate that IFN-γ suppresses both HBV propagation and transcription by activating specific intracellular signaling pathways in hepatocytes and suggests the future application of this particular signaling pathways or genes for the complete elimination of HBV.
2019-10-01 | GSE132628 | GEO
Project description:Objective: Curing hepatitis B requires the complete elimination of covalently closed circular DNA (cccDNA). Interferon (IFN)-γ is produced by cytotoxic T lymphocytes and has noncytolytic antiviral potential; however, elimination of cccDNA could not be achieved. To enhance the regulatory effect of IFN-γ, we comprehensively analyzed the host factors that associated with cccDNA amplification and IFN-γ effects using the in vitro HBV infection system that exhibits various transcription levels. Design: Primary human hepatocytes were infected with HBV using genomic plasmids carrying the basic core promoter 1762/1764 and/or the precore 1896 mutation and treated with IFN-γ, IFN-α, and entecavir. Comprehensive expression analysis and functional studies were performed to analyze the host factors related to the cccDNA regulation using RNA microarray and siRNA analysis. Results: HBV infection system accurately reproduced the HBV life cycle and exhibited various transcription levels. Microarray analysis revealed that 53 genes increased depending on the cccDNA levels. Of 53 genes, the expression of IFN-induced protein 44-like (IFI44L) was the most upregulated by IFN-γ and IFN-α but not entecavir, and associated with the anti-viral effects of IFN-γ. siRNA analysis revealed that IFI44L negatively regulates the innate immune response and IFN-γ function to suppress HBV transcription and propagation by inhibiting the activation of NF-κB and STAT1 pathways.
2020-12-12 | GSE163042 | GEO
Project description:Interferon gamma (IFN-γ) is the main cytokine driving Familial Hemophagocytic Lymphohistiocytosis (FHL) organ dysfunction. Hepatocytes are known to have IFN-γ receptor (IFN-γ-R). Blockade of IFN-γ pathway ameliorates FHL hepatitis, in animal models and in humans. However, whether IFN-γ induced hepatitis in FHL is a lymphocyte or liver intrinsic response to the cytokine has yet to be elucidated. We report that IFN-γ-mediated hepatic injury in the murine model of FHL is caused by direct effect on the liver and has a necessary role in recruitment of the inflammatory mediators of injury in FHL: inflammatory monocytes and CD8+ effector memory T lymphocytes (CD8+ CD44hi CD62Llo) (Tem).
2022-06-02 | GSE168086 | GEO
Project description:Gene expression profiling of primary human hepatocytes treated with IFN-alpha or IFN-gamma
| PRJNA168241 | ENA
Project description:Exosomes are extracellular vesicles that function in intercellular communication. We have previously reported that exosomes play a role in the transmission of antiviral molecules during interferon-α (IFN-α)-mediated immune responses. In this study, the protein contents of THP-1-derived macrophages with or without interferon-α treatment and of the exosomes secreted from these cells were analyzed by the label-free LC-MS/MS quantitation technologies. A total number of 1845 and 1550 protein groups were identified in the THP-1 macrophages and the corresponding exosomes, respectively. Treating the cells with IFN-α resulted in the differential abundance of 110 proteins in cells and 260 proteins in exosomes (greater than 2.0-fold), among which 35 proteins were both up-regulated in the IFN-α treated cells and corresponding exosomes while 139 proteins were specifically up-regulated in exosomes but not in the donor cells. GO and KEGG analysis of the protein function categories suggested that IFN-α promoted the abundance of proteins involved in “defense response to virus” in both exosomes and cells, and proteins related to “RNA processing” only in exosomes. Functional analysis further indicated that exosomes from IFN-α-treated cells exhibited potent antiviral activity that restored the impaired antiviral response of IFN-α in hepatitis B virus-replicating hepatocytes. These results have deepened the understanding of the exosome-mediated transfer of IFN-α-induced antiviral molecules and may provide new basis for therapeutic strategies to control viral infection.
2018-12-17 | PXD009746 | Pride
Project description:Human hepatocyte chimeric mice were prepared and treated with hepatitis C virus (HCV) and/or interferon-alpha (IFN-α). To analyze the changes in gene expression, cDNA microarray analysis was performed with the collected human hepatocytes from the chimeric mouse livers. We consider that these results provide molecular insights into possible mechanisms used by HCV to evade innate immune responses, as well as novel therapeutic targets and a potential new indication for interferon therapy.
2012-05-03 | GSE37715 | GEO