Identification of cytokine signals regulated by Caspase-9
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE57934 | GEO | 2014/11/03
SECONDARY ACCESSION(S): PRJNA248448
REPOSITORIES: GEO
Similar Datasets
Project description:Genome-wide transcriptional profiles of the hematopoietic stem and progenitor cell (HSPCs)-enriched population derived from bone marrow chimeras reconstituted with Caspase-9 or Bak and Bax deficient fetal liver cells. Gene ontology analysis revealed changes in the expression of genes associated with interferon responses. HSPCs (Lineage-Kit+CD45.2+) were flow sorted from the femur and tibia of bone marrow chimeras 12-16 weeks post transplant of 2 million embryonic day (E) 13.5 fetal liver cells. Total RNA was isolated and up to 250 ng of total RNA per sample was labelled and hybridized to Illumina Mouse WG6V2 expression BeadChip platform. Three independent samples were used for each population.
2014-11-03 | E-GEOD-57934 | biostudies-arrayexpress
Project description:Caspase-8 modulates TLR-induced gene transcription, which is only partially dependent on caspase-8 catalytic activity. Moreover, The slow kinetics of IFNγ and LPS-induced BMDM killing offers the possibility that transcriptional responses may contribute to cell death activation. We performed 3' mRNA-sequencing to examine whether caspase-8 might contribute, at least in part, to IFNγ and LPS-triggered macrophage death via its transcriptional role. We found that caspase-8-mediated transcriptional re-programming of BMDMs. Importantly, caspase-8 modulates expression of Bcl-2 family members and inducible nitric oxide synthase (iNOS) to promote activation of the mitochondrial apoptotic effectors, BAX and BAK.
2021-12-15 | GSE161179 | GEO
Project description:MEF WT, MEF DKO(Bax/Bak), MEF DKO(Bax/Bak) expressing rabbit Serca2a, MEF DKO(Bax/Bak) expressing Bak at the endoplasmic reticulum both control and treated with Noco 100 nM for 48h
2023-06-12 | E-MTAB-10997 | biostudies-arrayexpress
Project description:Pseudomonas aeruginosa use quorum-sensing molecules, including N-(3-oxododecanoyl)-homoserine lactone (C12), for intercellular communication. C12 activated apoptosis in mouse embryo fibroblasts (MEF) from both wild type (WT) and Bax/Bak double knock-out mice (WT MEF and DKO MEF that were responsive to C12, DKORM-BM- MEF): nuclei fragmented; mitochondrial membrane potential (M-bM-^HM-^FM-OM-^Hmito) depolarized; Ca2+M-BM- was released from the endoplasmic reticulum (ER), increasing cytosolic [Ca2+] (Cacyto); caspase 3/7 was activated. DKORM-BM- MEF had been isolated from a nonclonal pool of DKO MEF that were non-responsive to C12 (DKONRM-BM- MEF). RNAseq analysis, qPCR and western blots showed that WT and DKORM-BM- MEF both expressed genes associated with cancer, including paraoxonase 2 (PON2), while DKONRM-BM- MEF expressed little PON2. Adenovirus-mediated expression of human PON2 in DKONRM-BM- MEF rendered them responsive to C12: M-bM-^HM-^FM-OM-^HmitoM-BM- depolarized, CacytoM-BM- increased and caspase 3/7 activated. Human embryonic kidney 293T (HEK293T) cells expressed low levels of endogenous PON2, and these cells were also less responsive to C12. Overexpression of PON2, but not PON2-H114Q (no lactonase activity) in HEK293T cells caused them to become sensitive to C12. Because [C12] may reach high levels in biofilms in lungs of cystic fibrosis (CF) patients, PON2 lactonase activity may control M-bM-^HM-^FM-OM-^Hmito, Ca2+M-BM- release from the ER and apoptosis in CF airway epithelia. Coupled with previous data, these results also indicate that PON2 uses its lactonase activity to prevent Bax- and Bak-dependent apoptosis in response to common proapoptotic drugs like doxorubicin, staurosporine but activates Bax- and Bak-independent apoptosis in response to C12. Gene expression profiling of mouse embryo fibroblasts from WT and Bax/Bak double knock-out mice (C12 responsive and non-reponsive cell lines).
2015-02-14 | E-GEOD-65935 | biostudies-arrayexpress
Project description:Pseudomonas aeruginosa use quorum-sensing molecules, including N-(3-oxododecanoyl)-homoserine lactone (C12), for intercellular communication. C12 activated apoptosis in mouse embryo fibroblasts (MEF) from both wild type (WT) and Bax/Bak double knock-out mice (WT MEF and DKO MEF that were responsive to C12, DKOR MEF): nuclei fragmented; mitochondrial membrane potential (∆ψmito) depolarized; Ca2+ was released from the endoplasmic reticulum (ER), increasing cytosolic [Ca2+] (Cacyto); caspase 3/7 was activated. DKOR MEF had been isolated from a nonclonal pool of DKO MEF that were non-responsive to C12 (DKONR MEF). RNAseq analysis, qPCR and western blots showed that WT and DKOR MEF both expressed genes associated with cancer, including paraoxonase 2 (PON2), while DKONR MEF expressed little PON2. Adenovirus-mediated expression of human PON2 in DKONR MEF rendered them responsive to C12: ∆ψmito depolarized, Cacyto increased and caspase 3/7 activated. Human embryonic kidney 293T (HEK293T) cells expressed low levels of endogenous PON2, and these cells were also less responsive to C12. Overexpression of PON2, but not PON2-H114Q (no lactonase activity) in HEK293T cells caused them to become sensitive to C12. Because [C12] may reach high levels in biofilms in lungs of cystic fibrosis (CF) patients, PON2 lactonase activity may control ∆ψmito, Ca2+ release from the ER and apoptosis in CF airway epithelia. Coupled with previous data, these results also indicate that PON2 uses its lactonase activity to prevent Bax- and Bak-dependent apoptosis in response to common proapoptotic drugs like doxorubicin, staurosporine but activates Bax- and Bak-independent apoptosis in response to C12.
2015-02-14 | GSE65935 | GEO
Project description:Caspase-8 is a critical regulator of apoptosis, programmed necrosis, and inflammatory gene expression. Caspase-8 is necessary for optimal transcription of inflammatory and antimicrobial host defense genes, including Il12 and Il1b. While the mechanisms of caspase-8-mediated control of apoptosis and programmed necrosis are well-described, how caspase-8 controls inflammatory gene expression is less clear. We show that caspase-8 is necessary for optimal nuclear translocation of the NF-κB family member c-Rel, and consequently, for recruitment of c-Rel to caspase-8-dependent gene promoters. Furthermore, caspase-8 deficiency led to an inability to control acute Toxoplasma gondii infection. These findings provide new insight into how caspase-8 contributes to inflammatory gene expression and host defense.
2019-05-15 | GSE131171 | GEO
Project description:Intrinsic apoptosis is critical for normal physiology including the prevention of tumor formation. BAX and BAK, which are essential for mediating this process and for the cytotoxic action of many anti-cancer drugs, are thought to be regulated through similar mechanisms and act redundantly to drive apoptosis. Here we have established the various mitochondrial complexes that contain VDAC1, VDAC2, VDAC3 and BAX or BAK.
2018-10-29 | PXD011195 | Pride
Project description:The demonstration that mesenchymal stromal cells (MSCs) can ameliorate a wide range of diseases in preclinical models has led to many clinical trials investigating their use as a treatment modality. Their therapeutic effects are often attributed to their secretome, a proposition predicated on their long-term survival. However, the majority of MSCs do not survive in vivo administration. We sought to reconcile the immunosuppressive effects of MSC therapy with their short lifespan. We showed that almost all MSCs underwent apoptosis associated with caspase-3 activation within 1 hour of intravenous administration and were efferocytosed by lung phagocytes. The potent immunosuppressive effects of MSCs did not require them to remain viable, but instead involved efferocytosis-induced transcriptional changes in metabolic and inflammatory pathways in alveolar macrophages. We identified the mitochondrial pathway as the predominant mechanism involved in MSC apoptosis, as deletion of the effectors BAK/BAX prevented their death. Importantly, BAK/BAX deficiency in MSCs weakened their immunosuppressive effects in 2 different disease models used to define MSC potency. Our data showed that apoptosis of MSCs and their subsequent efferocytosis and macrophage immunometabolic reprogramming are key steps underlying their mode of action. These findings have significant implications for the development of MSC potency assays and biomanufacturing for clinical translation.
2021-09-16 | GSE156240 | GEO
Project description:Caspases regulate cell death programs in response to environmental stresses, including infection and inflammation, and are therefore critical for the proper operation of the mammalian immune system. Caspase-8 is necessary for optimal production of inflammatory cytokines and host defense against infection by multiple pathogens including Yersinia, but whether this is due to death of infected cells or an intrinsic role of caspase-8 in TLR-induced gene expression is unknown. Caspase-8 activation at death signaling complexes results in its autoprocessing and subsequent cleavage and activation of its downstream apoptotic targets. Whether caspase-8 activity is also important for inflammatory gene expression during bacterial infection has not been investigated. Here, we report that caspase-8 plays an essential cell-intrinsic role in innate inflammatory cytokine production in vivo during Yersinia infection. Unexpectedly, we found that caspase-8 enzymatic activity regulates gene expression in response to bacterial infection as well as TLR signaling independently of apoptosis. Using newly-generated mice in which caspase-8 autoprocessing is ablated (Casp8DA/DA), we now demonstrate that caspase-8 enzymatic activity, but not autoprocessing, mediates induction of inflammatory cytokines by bacterial infection and a wide variety of TLR stimuli. Because unprocessed caspase-8 functions in an enzymatic complex with its homolog cFLIP, our findings implicate the caspase-8/cFLIP heterodimer in control of inflammatory cytokines during microbial infection, and provide new insight into regulation of antibacterial immune defense.
2016-09-15 | GSE86922 | GEO