Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: BIOMD0000000501BIOMD0000000500
PROVIDER: PRJNA213916 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcriptional profiling of mouse primary embryonic fibroblasts (MEFs) from wild type (WT) and knockin littermates expressing STAT1F77A (KI). For both genotypes, untreated control cells were compared to cells treated with IFN-alpha or IFN-gamma.
2014-01-12 | GSE49441 | GEO
Project description:Transcriptional profiling of mouse primary embryonic fibroblasts (MEFs) from wild type (WT) and knockin littermates expressing STAT1F77A (KI). For both genotypes, untreated control cells were compared to cells treated with IFN-alpha or IFN-gamma. Two condition experiments; untreated versus IFN treated
2014-01-12 | E-GEOD-49441 | biostudies-arrayexpress
Project description:G-protein coupled receptors (GPCRs) have diverse roles in physiological processes, including immunity. Gs-coupled GPCRs increase while Gi-coupled ones decrease intracellular cAMP. Previous studies suggest that, in epithelial cells, Gs-coupled GPCRs enhance whereas Gi-coupled GPCRs suppress pro-inflammatory immune responses. In order to examine the issue, we chose beta2 adrenergic receptor and GPR40 as representatives of Gs- and Gi- coupled GPCRs, respectively, and examined their effects on TNF-alpha and IFN-gamma-(TNF-alpha + IFN-gamma) induced gene expression by HaCaT. We used microarrays to detail the global changes of gene expression induced by a beta2 adrenergic receptor agonist terbutaline or GPR40 agonist GW9508 pre-treatment in TNF-alpha + IFN-gamma - stimulated HaCaT cells. HaCaT cells were pre-treated with terbutaline or GW9508, TNF-alpha + IFN-gamma were then added, and cultured for another 24 h. Cells were then used for RNA extraction and hybridization on Affymetrix microarrays. We sought to clarify changes in gene expression after 1) TNF-alpha + IFN-gamma, 2) TNF-alpha + IFN-gamma + terbutaline, and 3) TNF-alpha + IFN-gamma + GW9508 treatment. To this end, we set 4 groups of samples; 1) unstimulated group, 2) TNF-alpha + IFN-gamma-stimulated group, 3) TNF-alpha + IFN-gamma + terbutaline-stimulated group, and 4) TNF-alpha + IFN-gamma + GW9508-stimulated group. In each group, HaCaT cells were stimulated in triplicate wells (n=3).
2010-12-01 | E-GEOD-20297 | biostudies-arrayexpress
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:Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/β-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/β immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-γ are, both quantitatively and qualitatively, much stronger than those to IFN-α/β. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-γ. By contrast, IFN-α/β-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-γ-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/β-dependent antiviral immunity.
2023-05-12 | GSE203220 | GEO
Project description:Interferon (IFN)-alpha causes high rates of depression and fatigue, and is used to investigate the impact of innate immune cytokines on brain and behavior. However, little is known about transcriptional profiles of circulating immune cells during chronic IFN-alpha administration. Accordingly, genome-wide transcriptional profiling was performed on peripheral blood mononuclear cells from 21 patients with chronic hepatitis C virus either awaiting IFN-alpha therapy (n=10) or after 12 weeks of IFN-alpha treatment (n=11). Significance analysis of microarray data identified 252 up-regulated gene transcripts, the majority of which were related to IFN-alpha/antiviral or innate-immune/inflammatory signaling. Of these upregulated genes, 2'-5'-oligoadenylate synthetase 2 (OAS2) was the only gene that was differentially expressed in patients that developed IFN-alpha-induced depression/fatigue, and correlated with depression and fatigue scores at 12 weeks of IFN-alpha administration. Promoter-based bioinformatic and cellular origin analyses revealed IFN-alpha-induced increases in genes bearing transcription factor binding motifs (TFBMs) related to myeloid differentiation, IFN-alpha signaling, API and CREB/ATF family of transcription pathways, with changes derived primarily from monocytes and plasmacytoid dendritic cells. Patients with high depression/fatigue scores demonstrated up-regulation of genes bearing TFBMs for myeloid differentiation, IFN-alpha and AP1 signaling, and down regulation of TFBMs for CREB/ATF-related transcription factors. Cellular origin analyses indicated a shift toward genes derived from CD8+T and NK cells in subjects with high depression/fatigue scores. These results reveal an antiviral and inflammatory transcriptional profile after 12 weeks IFN-alpha, accompanied by increased OAS2 expression, decreased CREB/ATF transcriptional control, and a shift from monocyte-derived genes to those of cytotoxic lymphocytes in IFN-alpha-induced depression/fatigue. Total RNA was isolated from the peripheral blood mononuclear cells (PBMC) obtained at 12 weeks from HCV patients treated with IFN-alpha plus ribavirin (n=11) and untreated HCV patients awaiting IFN-alpha/ribavirin therapy (control subjects, n=10).
2012-01-01 | E-GEOD-31187 | 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:Type-I (e.g. IFN-alpha, IFN-beta) and type-II IFNs (IFN-gamma) have antiviral, antiproliferative, and immunomodulatory properties. Both types of IFN signal through the Jak/STAT pathway to elicit antiviral activity, yet IFN-gamma is thought to do so only through STAT1 homodimers while type-I IFNs activate both STAT1- and STAT2-containing complexes such as ISGF3. Here we show that ISGF3II - composed of phosphorylated STAT1, unphosphorylated STAT2, and IRF9 - also plays a role in IFN-gamma-mediated antiviral activity in humans. Using phosphorylated STAT1 as a marker for IFN signaling, western blot analysis of IFN-alpha2a treated human A549 cells revealed that pSTAT1 (Y701) levels peaked at 1h, decreased by 6h, and remained at low levels for up to 48h. Cells treated with IFN-gamma showed a biphasic pSTAT1 response with an early peak at 1-2h and a second peak at 15-24h. Gene expression microarray following IFN-gamma treatment for 24h indicated an induction of antiviral genes that are induced by ISGF3 and associated with a type-1 IFN response. Induction of these genes by autocrine type-I and type-III IFN signaling was ruled out using neutralizing antibodies to these IFNs in biological assays and by qRT-PCR. Despite the absence of autocrine IFNs, IFN-gamma treatment induced formation of ISGF3II. This novel transcription factor complex binds to ISRE promoter sequences, as shown by ChIP analysis of the PKR promoter. STAT2 and IRF9 knockdown in A549 cells reversed IFN-gamma-mediated ISRE induction and antiviral activity - implicating ISGF3II formation as a significant component of the cellular response and biological activity of IFN-gamma. Two treatments using three biological replicates each were performed using three million A549 cells. Each was seeded overnight in 10mL complete RPMI and treated. Three were treated with alpha-IFN and three treated with gamma-IFN for 24h. Control samples were left untreated.
2011-01-19 | E-GEOD-25113 | biostudies-arrayexpress
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:Transcriptional response of KBM7 cells to IFN-gamma or TNF-alpha was investigated in control or cells with genetrap insertions in JAK2 or TNFRS1A, respectively. The experiment shows that, as expected, cells lacking JAK2 or TNFRS1A expression display a severly blunted response to the tested cytokines. KBM7 genetrap mutant cells stimulated with TNF-alpha and IFN-gamma Sample WT_1 corresponds with the control sample for the IFN-gamma stimulation; Sample WT_2 corresponds with the control sample for the TNF-alpha stimulation. As the expected differences between the samples was large, only single replicates were performed for each condition
2013-08-09 | E-GEOD-48848 | biostudies-arrayexpress