Genome-wide effect of ZBP1-mediated inflammatory response to LPS
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA801717 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17816513.fastq.gz | Fastqsanger.gz | |||
| SRR17816514.fastq.gz | Fastqsanger.gz | |||
| SRR17816515.fastq.gz | Fastqsanger.gz | |||
| SRR17816516.fastq.gz | Fastqsanger.gz | |||
| SRR17816517.fastq.gz | Fastqsanger.gz |
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Project description:We report the role of ZBP1 in mediating responses to LPS in the mouse macrophages.
2022-01-31 | GSE195687 | GEO
Project description:Cell death provides host defense and maintains homeostasis. Zα-containing molecules are essential for these processes. ZBP1 activates inflammatory cell death, PANoptosis, while ADAR1 serves as an RNA editor to maintain homeostasis. Here, we identify and characterize ADAR1’s interaction with ZBP1, defining its role in cell death regulation and tumorigenesis. Combining IFNs and nuclear export inhibitors (NEIs) activates ZBP1–dependent PANoptosis. ADAR1 suppresses PANoptosis by interacting with the Zα2 domain of ZBP1 to limit ZBP1 and RIPK3 interactions. Adar1fl/flLysMcre mice are resistant to development of colorectal cancer and melanoma, but deletion of the ZBP1 Zα2 domain restores tumorigenesis in these mice. In addition, treating wildtype mice with IFN-γ and the NEI KPT-330 regresses melanoma in a ZBP1–dependent manner. Our findings suggest that ADAR1 suppresses ZBP1–mediated PANoptosis, promoting tumorigenesis. Defining the functions of ADAR1 and ZBP1 in cell death is fundamental to inform therapeutic strategies for cancer and other diseases.
2021-10-19 | GSE184323 | GEO
Project description:ZBP1/IMP1 is an mRNA binding protein that post-transcriptionally regulates the expression of a handful mRNAs, implicated in maintaining cell polarity and adhesion. We have previously shown that ZBP1 was able to inhibit proliferation and invasiveness of breast carcinoma cells in vitro. In the current study, we utilized orthotopic breast fat pad xenografts to further investigate the ZBP1-mediated functions in breast tumorigenesis and metastasis in vivo. We used microarrays to identify important gene for breast tumor growth and metastasis in response to ZBP1 expression Total RNA was extracted from breast tumor generated from ZBP1-expression and ZBP1-nonexpression MDA231 cells and used for hybridization on Affymetrix microarrays. We sought to obtain gene expression profiles from the individual tumors and identify what genes are up-regulated or down-regulated in the presence of ZBP1. The microarray experiments and data analysis were performed in 'Gene Company Limited' in Senzheng, China. G-10 and G-13, Tumors generated from MDA231/GFP cells; I-5 and I-6, tumors generated from MDA231/ZBP1-GFP cells.
2014-10-24 | E-GEOD-62638 | biostudies-arrayexpress
Project description:ZBP1/IMP1 is an mRNA binding protein that post-transcriptionally regulates the expression of a handful mRNAs, implicated in maintaining cell polarity and adhesion. We have previously shown that ZBP1 was able to inhibit proliferation and invasiveness of breast carcinoma cells in vitro. In the current study, we utilized orthotopic breast fat pad xenografts to further investigate the ZBP1-mediated functions in breast tumorigenesis and metastasis in vivo. We used microarrays to identify important gene for breast tumor growth and metastasis in response to ZBP1 expression
2014-10-24 | GSE62638 | 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:The RNA editing enzyme ADAR1 is essential for suppression of innate immune activation and pathology caused by aberrant recognition of self-RNA, a role it carries out by disrupting the duplex structure of endogenous double-stranded RNA species. A point mutation in the Z-nucleic-acid binding domain (ZBD) of ADAR1 is associated with severe autoinflammatory disease. ZBP1 is the only other ZBD-containing mammalian protein and its activation can trigger both cell death and transcriptional responses via the kinases RIPK1 and RIPK3, and the protease caspase-8. Here, we show that the pathology caused by ADAR1 ZBD mutation is driven by activation of ZBP1. We found that ablation of ZBP1 fully rescued the overt pathology caused by ADAR1 mutation, without reversing the underlying inflammatory program caused by this mutation. While loss of RIPK3 partially phenocopied the protective effects of ZBP1 ablation, combined deletion of caspase-8 and RIPK3, or of caspase-8 and MLKL, unexpectedly exacerbated the pathogenic effects of ADAR1 mutation. These findings indicate that ADAR1 is a negative regulator of sterile ZBP1 activation, and that ZBP1-dependent signaling underlies the autoinflammatory pathology caused by mutation of ADAR1.
2022-06-11 | GSE200854 | GEO
Project description:The innate immune system recognizes nucleic acids as a signature of microbial infection and initiates host-protective responses, including the production of type I IFN and proinflammatory cytokines. Z-DNA binding protein 1 (ZBP1, also known as DLM-1 or DAI) was previously identified as a dsDNA binding protein, triggering DNA-mediated activation of innate immune responses. However, mice or cells lacking ZBP1 produce normal levels of type I IFN in response to dsDNA. Therefore, the classification of ZBP1 as a true DNA sensor remains to be resolved. Here, we report that the single stranded RNA virus, influenza A virus (IAV) is a trigger of the cytosolic sensor ZBP1. Sensing of IAV infection by ZBP1 engages a novel NLRP3 inflammasome pathway that is not defined by the conventions of the canonical and non-canonical NLRP3 inflammasome pathways. Surprisingly, IAV-induced cell death was not prevented by the absence of the NLRP3 inflammasome. Instead, we identified parallel contributions from pyroptosis, necroptosis and apoptosis in the execution of ZBP1-dependent cell death, mediated by the kinase RIPK3. Overall, the ability of ZBP1 to sense IAV infection signifies a point of divergence for IAV-induced programmed cell death pathways and inflammasome activation. We used microarrays to explore the gene expression profiles differentially expressed in influenza-infected bone marrow derived macrophages (BMDM) isolated from Ifnar1-/- and wild-type mice.
2016-08-11 | E-GEOD-77611 | biostudies-arrayexpress
Project description:B-cell lymphomas arising in Zbp1-/-Eu-Myc mice were compared to B-cell lymphomas arising in Zbp1+/+Eu-Myc mice
2014-04-01 | E-MTAB-2354 | biostudies-arrayexpress
Project description:Abstract Background & Aims: In liver transplantation, steatotic donor livers are rapidly increasing but are more susceptible to ischemia-reperfusion (I/R) injury. This study aimed to investigate the underlying mechanisms and identify therapeutic targets. Methods: Cell death markers were determined in donor livers and animal models. Casp8f/f;Alb-Cre, Ripk1D138N/D138N, Tnf-/-, Ripk3-/-, Trif-/-, Zbp1-/- mice were fed high fat diet or choline-deficient high fat diet to induce steatotic livers and were then subjected to I/R injury to investigate the mechanisms of cell death and inflammation. Primary mouse or human hepatocytes were isolated and subjected to hypoxia-reoxygenation challenge to further elucidate the regulation mechanisms. Results: Apoptosis- and inflammation-induced injury was exacerbated in I/R process of steatotic livers, with inflammation-induced injury playing a more predominant role. In both normal and steatotic livers, caspase-8 ablation mitigated I/R injury by reducing apoptosis but not inflammation while RIPK1 kinase inhibition more effectively protected against I/R injury by alleviating both apoptosis and inflammation. Z-DNA binding protein 1 (ZBP1) but not TNF-α deficiency inhibited RIPK1 activation and protected against I/R injury in steatotic livers but not normal livers. In steatotic livers, overmuch palmitic acid triggered ZBP1 transcription through activating JNK pathway. During liver transplantation, excessive reactive oxygen species were generated during I/R injury and triggered ZBP1 oligomerization, which led to the kinase activation of RIPK1 and the subsequent aggravation of apoptosis- and inflammation-induced injury. Conclusions: ZBP1-mediated apoptosis and inflammation exacerbate steatotic liver I/R injury, which could be leveraged to protect steatotic donor livers in transplantation.
2024-06-01 | GSE254747 | GEO
Project description:The RNA editing enzyme ADAR1 is essential for suppression of innate immune activation and pathology caused by aberrant recognition of self-RNA, a role it carries out by disrupting the duplex structure of endogenous double-stranded RNA species. A point mutation in the Z-nucleic-acid binding domain (ZBD) of ADAR1 is associated with severe autoinflammatory disease. ZBP1 is the only other ZBD-containing mammalian protein and its activation can trigger both cell death and transcriptional responses via the kinases RIPK1 and RIPK3, and the protease caspase-8. Here, we show that the pathology caused by ADAR1 ZBD mutation is driven by activation of ZBP1. We found that ablation of ZBP1 fully rescued the overt pathology caused by ADAR1 mutation, without reversing the underlying inflammatory program caused by this mutation. While loss of RIPK3 partially phenocopied the protective effects of ZBP1 ablation, combined deletion of caspase-8 and RIPK3, or of caspase-8 and MLKL, unexpectedly exacerbated the pathogenic effects of ADAR1 mutation. These findings indicate that ADAR1 is a negative regulator of sterile ZBP1 activation, and that ZBP1-dependent signaling underlies the autoinflammatory pathology caused by mutation of ADAR1.
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