Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene array analysis of WT and SKO macrophages following engulfment of irradiated HEK 293 cells with/without double-stranded DNA

ABSTRACT: The ability of dying cells to activate antigen presenting cells (APCs) is carefully controlled to avoid unwarranted inflammatory responses. Here we show that engulfed cells only containing cytosolic dsDNA species (viral or synthetic) or cyclic di-nucleotides (CDNs) are able to stimulate APCs, via extrinsic STING-signaling. HEK293 cells containing double strand DNA robustly induced the production of cytokines in macrophages that was dependent on extrinsic STING signaling within the macrophage.

ORGANISM(S): Mus musculus

PROVIDER: GSE110929 | GEO | 2018/09/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

SLC19A1 transports immunoreactive cyclic dinucleotides

Project description:The accumulation of DNA in the cytosol serves as a key immunostimulatory signal associated with infections, cancer and genomic damage. Cytosolic DNA triggers immune responses by activating the cGAS/STING pathway. The binding of DNA to the cytosolic enzyme cGAMP synthase (cGAS), activates its enzymatic activity, leading to the synthesis of a second messenger, cyclic[G(2’,5’)pA(3’,5’)] (2’3’-cGAMP). 2’3’-cGAMP, a cyclic dinucleotide (CDN), activates the protein ‘stimulator of interferon genes’ (STING), which in turn activates the transcription factors IRF3 and NF-κB promoting the transcription of genes encoding type I interferons and other cytokines and mediators that stimulate a broader immune response. Exogenous 2’3’-cGAMP produced by malignant cells and other CDNs, including CDNs produced by bacteria and synthetic CDNs used in cancer immunotherapy, must traverse the cell membrane to activate STING in target cells. How these charged CDNs pass through the lipid bilayer is unknown. Here we used a genome-wide CRISPR interference screen to identify the reduced folate carrier SLC19A1, a folate-organic phosphate antiporter, as the major transporter for CDNs. CDN uptake and functional responses are inhibited by depleting SLC19A1 from human cells and enhanced by overexpressing SLC19A1. In both human cell lines and primary cells ex vivo, CDN uptake is inhibited by folates, as well as two medications approved for treatment of inflammatory diseases, sulfasalazine and the antifolate methotrexate. The identification of SLC19A1 as the major transporter of CDNs into cells has implications for the immunotherapeutic treatment of cancer, host responsiveness to CDN-producing pathogenic microorganisms, and potentially in certain inflammatory diseases.

2019-09-01 | GSE134371 | GEO

Effect of PTTG on endogenous gene expression in HEK 293 cells.

Project description: Not available

| S-EPMC2793268 | biostudies-literature

Cholesterol down-regulates BK channels stably expressed in HEK 293 cells.

Project description: Not available

| S-EPMC3832390 | biostudies-literature

Clemizole hydrochloride blocks cardiac potassium currents stably expressed in HEK 293 cells.

Project description: Not available

| S-EPMC5241390 | biostudies-literature

Effects of chlorpyrifos and trichloropyridinol on HEK 293 human embryonic kidney cells.

Project description: Not available

| S-EPMC7462251 | biostudies-literature

The functional cooperation of 5-HT1A and mGlu4R in HEK-293 cell line.

Project description: Not available

| S-EPMC7550284 | biostudies-literature

Regulation of Kv4.2 A-Type Potassium Channels in HEK-293 Cells by Hypoxia.

Project description: Not available

| S-EPMC4196569 | biostudies-literature

Toxic effects of BDE209 in human embryonic kidney 293 cells (HEK 293)

Project description:PBDEs are widely used in consumer and household products as flame retardants. Many studies have shown that PBDEs could disrupt thyroid hormone homeostasis and adversely affect brain development. Here, we explored the toxical effects of BDE209 on HEK 293 cells and found that BDE209 may have a role in nucleosome remodeling. Many gene sets involved in cancer are enriched at the BDE209-treated sample. This indicates the carcinogenicity of BDE209. Interestingly, the impacts of BDE209 dissoved in DMSO on gene expression are more pronounced than the simple additive effects of BDE209 and DMSO alone. Gene expression profiles of human embryonic kidney 293 cells (HEK 293) cultured in normal medium, and medium containing BDE209 or DMSO were generated by deep sequencing, using Illumina HighSeq2000, respectively..

2014-04-21 | E-GEOD-56361 | biostudies-arrayexpress

Inflammation-Driven Carcinogenesis is Mediated through STING [skin]

Project description:Chronic stimulation of innate immune pathways by microbial agents or damaged tissue is known to promote inflammation-driven tumorigenesis by unclarified mechanisms1-3. Here we demonstrate that mutagenic 7,12-dimethylbenz(a)anthracene (DMBA), etoposide or cisplatin induces nuclear DNA leakage into the cytosol to intrinsically activate STING (Stimulator of Interferon Genes) dependent cytokine production. Inflammatory cytokine levels were subsequently augmented in a STING-dependent extrinsic manner by infiltrating phagocytes purging dying cells. Consequently, STING-/- mice, or wild type mice adoptively transferred with STING-/- bone marrow, were almost completely resistant to DMBA-induced skin carcinogenesis compared to their wild type counterparts. Our data emphasizes, for the first time, a role for STING in the induction of cancer, sheds significant insight into the causes of inflammation-driven carcinogenesis, and may provide therapeutic strategies to help prevent malignant disease Total RNA obtained from DMBA or acetone treated wild type (WT) or STING deficient (SKO) mouse skin or skin tumor was examined for gene expression.

2014-05-31 | E-GEOD-57604 | biostudies-arrayexpress

Rb interactome data and its modulations during cell cycle progression in HEK 293 cells.

Project description: Not available

| S-EPMC5852261 | biostudies-literature