Gene expression by cyotosolic DNA stimulation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE61835 | GEO | 2014/09/30
SECONDARY ACCESSION(S): PRJNA262515
REPOSITORIES: GEO
Similar Datasets
Project description:STING molecule has been reported to be important adaptor molecule for cytosolic DNA sensing. We investigated gene expression by cytosolic DNA stimulation using bone marrow derived dendritic cells. We comparared gene expression profile between WT and STING knock out BMDCs after cytosolic DNA stimulation. We generated BMDCs by culturing in the presence of GM-CSF. BMDCs were stimulated by purified tumor-cell derived DNA using lipofectamine. After 7 hrs incubation, total RNA was isolated using Rneasy kit (Qiagen) and microarray was performed at genomic core facility in university of Chicago
2014-09-30 | E-GEOD-61835 | biostudies-arrayexpress
Project description:The transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is activated by the metabolite itaconate during metabolic reprogramming. Activated Nrf2 then dampens the release of pro-inflammatory cytokines and type I IFNs in response to toll-like receptor stimulation. If and how Nrf2 affects cytosolic antiviral sensing and whether this occurs during metabolic reprogramming is currently not known. Here, we show that Nrf2 is a negative regulator of the adaptor molecule STimulator of INterferon Genes (STING), which signals downstream of the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS). The regulation of STING by Nrf2 was inducible by the metabolite itaconate, specific to human cells, and sufficient to decrease the responsiveness to STING agonists and to increase the susceptibility to infection with DNA viruses. Mechanistically, Nrf2 regulated STING expression post-transcriptionally by increasing STING mRNA stability. Lastly, treatment with itaconate or with the chemical Nrf2 inducer sulforaphane repressed STING expression and the release of type I IFNs in cells from patients with the STING dependent interferonopathy SAVI. With this report we identify Nrf2 as an important regulator of cGAS-STING signaling pathway and link metabolic reprogramming to control of cytosolic DNA sensing.
2018-05-01 | GSE113519 | GEO
Project description:Gene expression analysis of dsDNA90 stimulated human telomerase fibroblasts (hTERT-BJ1) after STING siRNA treatment. Genes whose expression that are affected by cytosolic DNA in a STING dependent manner will be identified and signaling pathways regulated by STING will be elucidated. hTERT-BJ1 cells were transfected with non-specific or STING siRNA for 72 hours followed by dsDNA90 stimulation for 3 hours. Total RNA was extracted for array analysis.
2013-01-15 | E-GEOD-43480 | biostudies-arrayexpress
Project description:Nitidine Chloride(NC) were found to enhance IL-10 production in LPS-stimulated Bone-marrow dendritic cells(BMDCs ) ,while at the same time inhibit pro-inflammatory cytokines production, such as TNF- α and IL-6. BMDCs were treated with NC or vehicle following LPS stimulation to find out the influence of NC on BMDCs that regulate cytokines expression. This study indicated that NC regulate numerous gene expression, thus influence IL-10 and pro-inflammatory cytokines production in LPS-treated BMDCs.
2017-08-05 | GSE102135 | GEO
Project description:Ionizing radiation promotes cytosolic DNA sensing and consequent antitumor immune responses. But how tumor cell-intrinsic cytosolic DNA sensing is initiated by radiation remains poorly defined. Here, we demonstrated that STING-mediated type I interferon production in tumor cells after radiation relied on the engagement of MLKL-mediated necroptosis, which was elicited by the ZBP1-RIPK3 signaling axis. Physiologically, tumor cell-intrinsic ZBP1-MLKL cascade augmented antitumor immune responses after radiation largely by regulating STING signaling. Mechanistically, ZBP1-MLKL-dependent necroptosis maintained the enrichment of mitochondria DNA inside the cytosol of tumor cells after radiation in a cell-density dependent fashion, contributing to type I interferon responses. In contrast, ablation of caspase-8 unleashed ZBP1-MLKL cascade to gain enhanced cytosolic DNA sensing, and in turn potentiated therapeutic effects of radiation. Thus, our findings uncover an unanticipated mechanism that ZBP1-MLKL-dependent necroptosis drives cytosolic DNA sensing-mediated antitumor immunity after radiation, and provide new strategy to improve radiotherapy by inhibiting caspase-8 cascade.
2021-10-13 | GSE168016 | GEO
Project description:Mounting evidence demonstrates that cGAS-STING signaling is the major pathway in sensing cytosolic DNAs. However, aberrant accumulation of self DNA molecules in Trex1 (a 3'-to-5' DNA exonuclease) deficient cells usually causes over-activation of cGAS-STING signaling, which is associated with the pathology of several autoimmune diseases. Here, we investigated gene expression changes in BMDM cells of Trex1 knockout mice after manipulating cGAS-STING signaling activity via treatment of two STING antagonists (SN-011 and H151) .
2021-05-26 | GSE143830 | GEO
Project description:Inflammasomes are critical for mounting host defense against pathogens. The molecular mechanisms that control activation of the AIM2 inflammasome in response to different cytosolic pathogens remain unclear. Here we found that the transcription factor IRF1 was required for the activation of the AIM2 inflammasome during infection with the Francisella tularensis subspecies novicida (F. novicida), whereas engagement of the AIM2 inflammasome by mouse cytomegalovirus (MCMV) or transfected double-stranded DNA did not require IRF1. Infection of F. novicida detected by the DNA sensor cGAS and its adaptor STING induced type I interferon-dependent expression of IRF1, which drove the expression of guanylate-binding proteins (GBPs); this led to intracellular killing of bacteria and DNA release. Our results reveal a specific requirement for IRF1 and GBPs in the liberation of DNA for AIM2 sensing depending on the pathogen encountered by the cell. We used microarrays to explore the gene expression profiles differentially expressed in Francisella-infected bone marrow-derived macrophages (BMDMs) isolated from Irf1-/-, Ifnar1-/-, Aim2-/- and wild-type mice.
2015-03-04 | E-GEOD-66461 | biostudies-arrayexpress
Project description:Dendritic cells (DC) play central roles in coordinating appropriate immune responses to pathogens. In the present study, the genes regulated by NFkB activators, RelB and cRel, in PAMP-induced bone marrow dendritic cells (BMDCs) activation was examined. Total RNA extracted from WT, relb-/-, crel-/-relb-/- bone marrow derived dendritic cells (BMDCs) were subjected to stimulation with CpG or Pam3CSK4.
2012-10-01 | E-GEOD-34990 | biostudies-arrayexpress
Project description:We report positional cloning and characterization of a novel Sting allele that fails to activate IFN production in the wild-derived mice of MOLF/Ei strain in response to HSV (Herpes Simplex Virus) and Listeria monocytogenes both in vitro and in vivo. We show that previously uncharacterized mutations in the N-terminal of STING are responsible for low levels of IFN due to failure of MOLF STING to respond to cytosolic STING agonists such as 2â3âcGAMP, 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) or poly(deoxyadenylic-deoxythymidylic) acid (dAdT). Using Next-Generation Sequencing (NGS) for the analysis of DNA-responses in congenic C57BL6.StingMOLF/MOLF (MOLF STING) mouse macrophages, we show that these mutations in MOLF/Ei discriminate in responses between different STING agonists. Macrophages from C57BL6.StingB6/B6¬ (B6 STING), or B6 STING expressing littermates were stimulated as a positive control for STING activation, and STING -/- (STING KO) macrophages served as a negative control. To examine differential gene regulation downstream of murine Tmem173 (STING) allelic variants. We stimulated macrophages from B6 mice congenic for MOLF STING; macrophages from B6 STING expressing littermates were stimulated as a positive control for STING activation, and STING -/- (STING KO) macrophages served as a negative control. One replicate of RNA-seq reads after each stimulation provided. Conditions are peritoneal macrophages from B6 congenic mice expressing: B6 STING, MOLF STING, or STING KO stimulated with 2â3âcGAMP, 5,6-Dimethylxanthenone-4-acetic acid (DMXAA), poly(deoxyadenylic-deoxythymidylic) acid (dAdT), or no treatment. This constitutes a total of 12 reads analyzed in this data set.
2016-07-05 | E-GEOD-68140 | biostudies-arrayexpress
Project description:Inflammasomes are critical for mounting host defense against pathogens. The molecular mechanisms that control activation of the AIM2 inflammasome in response to different cytosolic pathogens remain unclear. Here we found that the transcription factor IRF1 was required for the activation of the AIM2 inflammasome during infection with the Francisella tularensis subspecies novicida (F. novicida), whereas engagement of the AIM2 inflammasome by mouse cytomegalovirus (MCMV) or transfected double-stranded DNA did not require IRF1. Infection of F. novicida detected by the DNA sensor cGAS and its adaptor STING induced type I interferon-dependent expression of IRF1, which drove the expression of guanylate-binding proteins (GBPs); this led to intracellular killing of bacteria and DNA release. Our results reveal a specific requirement for IRF1 and GBPs in the liberation of DNA for AIM2 sensing depending on the pathogen encountered by the cell.
2015-03-04 | GSE66461 | GEO