Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA141071 | ENA |
REPOSITORIES: ENA
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Project description:Clinical applications of human interferon (IFN)-alpha have met with varying degrees of success. Nevertheless, key molecules in IFN-alpha-induced cell death have not been clearly identified. Our previous study indicated that IFN (alpha, beta and omega) receptor (IFNAR) 1/2- and IFN regulatory factor (IRF) 9-RNA interference (RNAi) completely inhibited the antiproliferative (AP) activity of IFN-alpha in human ovarian adenocarcinoma OVCAR3 cells sensitive to IFN-alpha., followed by transcription of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Here, IFNAR1/2- and IRF9-RNAi inhibited the gene expression of TRAIL, but not of Fas ligand (FasL), following IFN-alpha treatment. In fact, TRAIL but not FasL inhibited the proliferation of OVCAR3 cells. IFN-alpha notably up-regulated the levels of TRAIL protein in the supernatant and on the membrane of OVCAR3 cells. Following TRAIL signaling, Caspase 8 inhibitor and BH3 interacting domain death agonist (BID)-RNAi significantly abrogated both AP activities of IFN-alpha and TRAIL. Furthermore, BID-RNAi prevented both IFN-alpha and TRAIL from collapsing the mitochondrial membrane potential (Delta Psi m). Finally, we provide important new evidence that BID overexpression led to a major enhancement of both AP activities of IFN-alpha and TRAIL in human lung carcinoma A549 cells resistant to IFN-alpha. Thus, this study suggests that BID is crucial in IFN-alpha-induced cell death, indicating a notable potential to be a targeted therapy for IFN-alpha resistant tumors. Biological replicate samples were created by treating OVCAR3 cells with IFN-alpha2c (n=8); IFNAR1-RNAi and IFN-alpha2c (n=4); IFNAR2-RNAi and IFN-alpha2c (n=5); ISGF3gamma-RNAi and IFN-alpha2c (n=3); and Negative RNAi and IFN-alpha2c (n=3). For analysis, the eight IFN-alpha2c treated OVCAR3 samples were paired with an untreated OVCAR3 control sample. The 15 RNAi treated OVCAR3 samples were paired with a Negative RNAi control sample.
2012-05-21 | E-GEOD-29790 | biostudies-arrayexpress
Project description:Clinical applications of human interferon (IFN)-alpha have met with varying degrees of success. Nevertheless, key molecules in IFN-alpha-induced cell death have not been clearly identified. Our previous study indicated that IFN (alpha, beta and omega) receptor (IFNAR) 1/2- and IFN regulatory factor (IRF) 9-RNA interference (RNAi) completely inhibited the antiproliferative (AP) activity of IFN-alpha in human ovarian adenocarcinoma OVCAR3 cells sensitive to IFN-alpha., followed by transcription of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Here, IFNAR1/2- and IRF9-RNAi inhibited the gene expression of TRAIL, but not of Fas ligand (FasL), following IFN-alpha treatment. In fact, TRAIL but not FasL inhibited the proliferation of OVCAR3 cells. IFN-alpha notably up-regulated the levels of TRAIL protein in the supernatant and on the membrane of OVCAR3 cells. Following TRAIL signaling, Caspase 8 inhibitor and BH3 interacting domain death agonist (BID)-RNAi significantly abrogated both AP activities of IFN-alpha and TRAIL. Furthermore, BID-RNAi prevented both IFN-alpha and TRAIL from collapsing the mitochondrial membrane potential (Delta Psi m). Finally, we provide important new evidence that BID overexpression led to a major enhancement of both AP activities of IFN-alpha and TRAIL in human lung carcinoma A549 cells resistant to IFN-alpha. Thus, this study suggests that BID is crucial in IFN-alpha-induced cell death, indicating a notable potential to be a targeted therapy for IFN-alpha resistant tumors.
2012-05-22 | GSE29790 | GEO
Project description:IFN alpha-induced gene expression in human NK cells
| PRJNA116885 | ENA
Project description:Dysregulation of professional APC has been postulated as a major mechanism underlying Ag-specific T cell hyporesponsiveness in patients with patent filarial infection. To address the nature of this dysregulation, dendritic cells (DC) and macrophages generated from elutriated monocytes were exposed to live microfilariae (mf), the parasite stage that circulates in blood and is responsible for most immune dysregulation in filarial infections. DC exposed to mf for 24â96 h showed a marked increase in cell death and caspase-positive cells compared with unexposed DC, while mf exposure did not induce apoptosis in macrophages. Interestingly, 48 h exposure of DC to mf induced mRNA expression of the pro-apoptotic gene TRAIL and both mRNA and protein expression of TNF-alpha. mAb to TRAIL-R2, TNF-R1, or TNF-alpha partially reversed mf-induced cell death in DC, as did knocking down the receptor for TRAIL-R2 using small interfering RNA. Mf also induced gene expression of BH3-interacting domain death agonist (Bid) and protein expression of cytochrome c in DC; mf-induced cleavage of Bid could be shown to induce release of cytochrome c, leading to activation of caspase 9. Our data suggest that mf induce DC apoptosis in a TRAIL- and TNF-alpha-dependent fashion. Experiment Overall Design: Microfilariae and human monocyte derived-DCs were cultuted at a multiplicity of infection of 1:1 for 24hrs for four independent donors. Matching samples exposed to media alone were used for controls The four experimental and 4 control samples were then pooled to create one experoimental and one healthy pool used for microarray analysis.
2008-10-25 | E-GEOD-12787 | biostudies-arrayexpress
Project description: Not available
| S-EPMC2531291 | biostudies-literature
Project description:Dysregulation of professional APC has been postulated as a major mechanism underlying Ag-specific T cell hyporesponsiveness in patients with patent filarial infection. To address the nature of this dysregulation, dendritic cells (DC) and macrophages generated from elutriated monocytes were exposed to live microfilariae (mf), the parasite stage that circulates in blood and is responsible for most immune dysregulation in filarial infections. DC exposed to mf for 24–96 h showed a marked increase in cell death and caspase-positive cells compared with unexposed DC, while mf exposure did not induce apoptosis in macrophages. Interestingly, 48 h exposure of DC to mf induced mRNA expression of the pro-apoptotic gene TRAIL and both mRNA and protein expression of TNF-alpha. mAb to TRAIL-R2, TNF-R1, or TNF-alpha partially reversed mf-induced cell death in DC, as did knocking down the receptor for TRAIL-R2 using small interfering RNA. Mf also induced gene expression of BH3-interacting domain death agonist (Bid) and protein expression of cytochrome c in DC; mf-induced cleavage of Bid could be shown to induce release of cytochrome c, leading to activation of caspase 9. Our data suggest that mf induce DC apoptosis in a TRAIL- and TNF-alpha-dependent fashion. Keywords: Dendritic Cell, Parasite, Human, Microfilariae
2008-09-17 | GSE12787 | GEO
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:Genetic variation in radiation-induced cell death
| PRJNA136043 | ENA
Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes
2014-08-06 | GSE58734 | GEO