Microarray data of human moDC treated with IFNβ and TNFα
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE134209 | GEO | 2020/11/30
REPOSITORIES: GEO
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Project description:Microarray data of human moDC treated with IFNβ and TNFα
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Project description:Interferon (IFN) β and Tumor Necrosis Factor (TNF) α are key players in immunity against pathogens as well as in the development of autoinflammatory and autoimmune diseases. Accordingly, their molecular pathways have attracted much interest as therapeutic targets. Compelling evidence has shown that the antiviral and inflammatory transcriptional response induced by IFNβ is reprogrammed by crosstalk with TNFα. IFNβ typically induces interferon-stimulated genes by the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway leading to activation of the canonical ISGF3 transcriptional complex, composed of STAT1, STAT2 and IRF9. The signaling pathways engaged downstream of the combination of IFNβ and TNFα remain elusive, but previous observations suggested the existence of a response independent of STAT1. Here, using genome-wide transcriptional analysis by RNASeq, we observed a broad antiviral and immunoregulatory response initiated in the absence of STAT1 upon IFNβ and TNFα costimulation. Additional stratification of this transcriptional response with respect to the role of STAT2 and IRF9 revealed that they mediate the expression of a wide spectrum of genes. While a subset of genes was regulated by the concerted action of STAT2 and IRF9, other gene sets were independently regulated by STAT2 or IRF9. Collectively, our data supports a model in which STAT2 and IRF9 act through non-canonical parallel pathways to regulate distinct pool of genes in response to IFNβ and TNFα. This study provides novel insights into the molecular pathways leading to antiviral and immunoregulatory gene expression in conditions where elevated levels of both IFNβ and TNFα are present.
2018-02-28 | GSE111195 | GEO
Project description:The current project is designed to evaluate the utility of proteomics in identifying pharmacodynamic (PD) biomarkers for biosimilarity assessment. This is an extension of the data submitted in GSE207945 which profiled longitudinal plasma samples from healthy subjects treated with single therapeutic doses/high doses of IFNβ-1a (30 μg) or Pegylated IFNβ-1a (125 μg) or placebo, to identify candidate PD biomarkers for the two biologics (n=248 for IFNβ-1a and N=528 for pegIFNβ-1a). The current project is a continuation study profiling longitudinal plasma samples from healthy subjects treated with a low dose of IFNβ-1a (7.5 μg) and pegIFNβ-1a (31.25 μg). In the current study, we reproduced the previous PD biomarker candidate responses at an intermediate/lower dose IFNβ-1a (15 μg) and pegIFNβ-1a (62.5 μg), and further characterized their PD response using characteristics such as significant area under the effect curve, dose-response, temporal profile and return to baseline, variability and sensitivity of the biomarker with sensitive doses on the steep portion of the dose-response curve and mechanism of action using the three tested dose-groups (high, intermediate and low) in the study.
2026-06-23 | GSE300489 | GEO
Project description:The current project is designed to evaluate the utility of proteomics in identifying pharmacodynamic (PD) biomarkers for biosimilarity assessment. This is an extension of the data submitted in GSE207945 which profiled longitudinal plasma samples from healthy subjects treated with single therapeutic doses/high doses of IFNβ-1a (30 μg) or Pegylated IFNβ-1a (125 μg) or placebo, to identify candidate PD biomarkers for the two biologics (n=248 for IFNβ-1a and N=528 for pegIFNβ-1a). The current project is a continuation study profiling longitudinal plasma samples from healthy subjects treated with an intermediate/lower dose of IFNβ-1a (15 μg) and pegIFNβ-1a (62.5 μg). Here, we reproduced the previous PD biomarker candidate responses at a lower dose, and further characterized their PD response using characteristics such as significant area under the effect curve, dose-response, temporal profile and return to baseline, variability and sensitivity of the biomarker with sensitive doses on the steep portion of the dose-response curve and mechanism of action using all three tested dose groups (high, intermediate and low).
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Project description:Control, TNFα and TNFα+JNK I treated GSCs
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Project description:To investigate the gene expression of MoDC after PRRSV stimulation and nucleocapsid protein transfection
2016-08-30 | GSE86182 | GEO
Project description:Epstein-Barr virus (EBV) persistently infects over 90% of the human population and is the causative agent of infectious mononucleosis and human cancers. For the establishment of life-long infection, EBV tampers with the induction of type I interferon (IFN I)-dependent antiviral immunity in the host. How various EBV latency genes help orchestrate this crucial strategy is incompletely defined. Here, we reveal the mechanism by which the EBV nuclear antigen 3A (EBNA3A) inhibits IFNβ induction. Using proximity biotinylation we identify the histone acetyltransferase P300, a member of the IFNβ transcription complex, as a binding partner of EBNA3A. Follow-up experiments further demonstrate that EBNA3A also interacts with the activated IFN-inducing transcription factor IRF3 that collaborates with P300 in the nucleus and both events are mediated by the N-terminal domain of EBNA3A. Mechanistic studies reveal that EBNA3A reduces the binding of IRF3 to the IFNβ promotor, thereby hampering downstream IFN I signaling. These results reveal a novel mechanism by which viral immune evasion takes place.
2025-05-06 | PXD038572 | Pride
Project description:Cellular senescence is a key cell-fate program that leads to an essentially irreversible proliferative arrest in potentially damaged cells. Cytokine production and signaling play a significant role in senescence. Tumor necrosis factor-alpha (TNFα), an important pro-inflammatory cytokine secreted by some senescent cells, can induce senescence in mouse and human cells. However, downstream signaling pathways and key regulatory genes linking inflammation to senescence are not fully characterized. Using human umbilical vein endothelial cells (HUVECs) as a model, we show TNFα induces permanent growth arrest and increased senescence markers such as p21, p16, and senescence-associated β-galactosidase (SA-β-gal), accompanied by persistent DNA damage and ROS. By gene expression profiling and pathway analysis, we identify the crucial involvement of inflammatory networks, an interferon signature, and persistent activation of the Janus kinase (JAK) /signal transducer and activator of transcription (STAT) pathway in TNFα-mediated senescence. TNFα initiates a STAT-dependent autocrine loop leading to sustained inflammation, DNA damage, and expression of interferon response genes to lock cells into senescence. Further, we show STAT1/3 activation is necessary for cytokine and ROS production during TNFα-induced senescence. However, inhibition of STAT1/3 did not rescue cells from TNFα-mediated senescence. Rather, blockade of STAT activation accelerated senescence, suppressed genes that control the cell cycle, and modulated TNFα-induced senescence. Our findings suggest a positive feedback mechanism via a STAT pathway that sustains cytokine production and reveal a reciprocal regulatory role of JAK/STAT in TNFα-mediated senescence.
2017-04-24 | GSE98081 | GEO
Project description:Cellular senescence is a key cell-fate program that leads to an essentially irreversible proliferative arrest in potentially damaged cells. Cytokine production and signaling play a significant role in senescence. Tumor necrosis factor-alpha (TNFα), an important pro-inflammatory cytokine secreted by some senescent cells, can induce senescence in mouse and human cells. However, downstream signaling pathways and key regulatory genes linking inflammation to senescence are not fully characterized. Using human umbilical vein endothelial cells (HUVECs) as a model, we show TNFα induces permanent growth arrest and increased senescence markers such as p21, p16, and senescence-associated β-galactosidase (SA-β-gal), accompanied by persistent DNA damage and ROS. By gene expression profiling and pathway analysis, we identify the crucial involvement of inflammatory networks, an interferon signature, and persistent activation of the Janus kinase (JAK) /signal transducer and activator of transcription (STAT) pathway in TNFα-mediated senescence. TNFα initiates a STAT-dependent autocrine loop leading to sustained inflammation, DNA damage, and expression of interferon response genes to lock cells into senescence. Further, we show STAT1/3 activation is necessary for cytokine and ROS production during TNFα-induced senescence. However, inhibition of STAT1/3 did not rescue cells from TNFα-mediated senescence. Rather, blockade of STAT activation accelerated senescence, suppressed genes that control the cell cycle, and modulated TNFα-induced senescence. Our findings suggest a positive feedback mechanism via a STAT pathway that sustains cytokine production and reveal a reciprocal regulatory role of JAK/STAT in TNFα-mediated senescence.
2017-03-10 | GSE92655 | GEO
Project description:Type-I interferon signalling plays a critical role in immunity especially during viral infections. IFNAR1-deficent macrophages are highly resistant to Salmonella typhimurium (ST) infection and to the stimulation with LPS, poly I:C and TNFα. We have used microarray expression profiling on bone marrow derived macrophage cells as a discovery platform to identify genes that play a role in their resistance. Several genes were identified downregulated in IFNAR1-deficient macrophages compared to WT control sample. The Expression of identified genes will be quantified by qRT-PCR followed by knockdown of identified genes using si-RNA approach. The identified genes will help us to understand how IFNβ mediates susceptibility to bacterial infection in macrophages.
2024-08-15 | GSE134549 | GEO