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IFN-alpha Stimulated Gene Expression in Sensitive and Resistant Renal Cell Carcinoma Cell Lines

ABSTRACT: The antiproliferative, antiviral, and immunomodulatory properties of interferons (IFNs) have led to its therapeutic implementation. IFNs effects are mediated by a complex network of signal transducers, culminating in IFN-stimulated gene (ISG) induction. This complexity leads to diverse clinical responses to IFN, from no response to complete regression of disease. Elucidation of ISG induction patterns is, therefore, essential to understand and maximize its therapeutic potential. To correlate ISG expression profiles with IFN responsiveness, two renal cell carcinoma (RCC) cell lines differing in antiviral and apoptotic response to IFN were treated with IFN-alpha for different times, and expression profiles were analyzed using a customized microarray containing 850 unique putative ISGs. Genes with similar kinetics of induction in both cell lines were clustered and analyzed for gene function. Seven sets of coordinately regulated genes were identified by k-means cluster analysis, and significant functional similarities were identified for five of the seven sets. Strikingly, expression of genes associated with transcription temporally preceded expression of those involved in signal transduction. Enhanced antiviral sensitivity to IFN was coincident with sustained expression of ISGs involved in transcriptional regulation. However, no difference in Stat1 activation was observed between the cell lines. Analysis of ISG expression patterns suggests that subtle differences in transcription profiles contribute to differences in IFN responsiveness.

ORGANISM(S): Homo sapiens

PROVIDER: GSE15193 | GEO | 2009/05/22

SECONDARY ACCESSION(S): PRJNA123133

REPOSITORIES: GEO

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IFN-alpha Stimulated Gene Expression in Sensitive and Resistant Renal Cell Carcinoma Cell Lines

Project description:The antiproliferative, antiviral, and immunomodulatory properties of interferons (IFNs) have led to its therapeutic implementation. IFNs effects are mediated by a complex network of signal transducers, culminating in IFN-stimulated gene (ISG) induction. This complexity leads to diverse clinical responses to IFN, from no response to complete regression of disease. Elucidation of ISG induction patterns is, therefore, essential to understand and maximize its therapeutic potential. To correlate ISG expression profiles with IFN responsiveness, two renal cell carcinoma (RCC) cell lines differing in antiviral and apoptotic response to IFN were treated with IFN-alpha for different times, and expression profiles were analyzed using a customized microarray containing 850 unique putative ISGs. Genes with similar kinetics of induction in both cell lines were clustered and analyzed for gene function. Seven sets of coordinately regulated genes were identified by k-means cluster analysis, and significant functional similarities were identified for five of the seven sets. Strikingly, expression of genes associated with transcription temporally preceded expression of those involved in signal transduction. Enhanced antiviral sensitivity to IFN was coincident with sustained expression of ISGs involved in transcriptional regulation. However, no difference in Stat1 activation was observed between the cell lines. Analysis of ISG expression patterns suggests that subtle differences in transcription profiles contribute to differences in IFN responsiveness. Two human renal cell carcinoma cell lines (ACHN and RCC1) were treated with IFN-alpha for 3, 6, 9, 12, 16, and 24 hours. Total RNA from treated cells (Cy5) is hybridized with total RNA from untreated control cells (Cy3) to the custom ISG 1.3.1 cDNA array.

2010-05-18 | E-GEOD-15193 | biostudies-arrayexpress

Primary human hepatocytes treated with IFNalpha and IL28B

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Transcription profiling by array of primary human hepatocytes derived from hepatitis C patients treated with type III interferons (IFNs) for 6 or 24 hours

Project description:Recent identification of IL28B gene polymorphisms associated with hepatitis C virus (HCV) clearance suggests a role for type III interferons (IFNs) in hepatitis C infection. The function of type III IFNs in intrinsic antiviral immunity is poorly understood. Here we show that HCV infection of primary human hepatocytes results in a robust induction of type III but not type I IFNs, leading to IFN- stimulated gene (ISG) expression. In addition, HCV infection elicits a much broader range of gene expression alterations in addition to ISG induction. The induction of type III IFNs is mediated by IRF3 and NFkB- dependent pathways. Type III IFN, aside from upregulating ISGs with a different kinetic profile, induces a distinct set of genes from type I IFN, potentially explaining the functional difference between the two types of IFNs. Chimpanzees undergoing experimental HCV infection demonstrated a prompt hepatic induction of IL28, associating with ISG upregulation, but minimal type I IFN induction. Analysis of liver biopsies from HCV-infected patients supported a close correlation among hepatic expression of IL28 and ISGs, but not with type I IFNs. Our study demonstrates that HCV infection results predominantly in type III IFN induction in the liver and the level of induction correlates with hepatic ISG levels, thus providing a mechanistic explanation for the association between IL28, ISG levels and recovery from HCV infection as well as a potential therapeutic strategy for the treatment of non-responders. Samples were treated with IFN or IL28b after 6 or 24 hours with three replications

2012-03-09 | E-GEOD-31193 | biostudies-arrayexpress

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2013-08-16 | E-GEOD-31455 | biostudies-arrayexpress

Stage-specific IFN-induced and IFN gene expression reveals convergence of type I and type II IFN and highlights their role in both acute and chronic phases of pathogenic SIV infection

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Primary human hepatocytes treated with IFNalpha and IL28B

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Primary human hepatocytes treated with IL28B and the HCV JFH1 Genotype 2A clone.

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Dynamic expression profiling of type I and type III interferon-stimulated hepatocytes.

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