Dental pulp cell-derived powerful inducer of TNF-alpha comprises PKR containing stress granule rich microvesicles
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ABSTRACT:
PROVIDER: PRJNA512198 | ENA |
REPOSITORIES: ENA
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Project description:Dental pulp cell-derived powerful inducer of TNF-alpha comprises PKR containing stress granule rich microvesicles (pDCvsGF)
| PRJNA512199 | ENA
Project description:It is well known that dental pulp tissue can evoke some of the most severe acute inflammation observed in the human body. We found that dental pulp cells secrete a factor that induces tumor necrosis factor-α production from macrophages, and designated this factor, dental pulp cell-derived tumor necrosis factor-α-inducing factor (DPTIF). DPTIF was induced in dental pulp cells and transported to recipient cells via microvesicles. Treatment of dental pulp cells with a PKR inhibitor markedly suppressed DPTIF activity, and weak interferon signals were constitutively activated inside the cells. In recipient macrophages, stimulation with DPTIF-containing supernatants from pulp cells resulted in activation of both nuclear factor-κB and MAP kinases like JNK and p38. Proteomics analyses revealed that many stress granule-related proteins were present in supernatants from dental pulp cells as well as microvesicle marker proteins like GAPDH, β-actin, HSPA8, HSPB1, HSPE1, and HSPD1. Furthermore, giant molecule AHNAK and PKR were detected in microvesicles derived from dental pulp cells, and gene silencing of AHNAK in pulp cells led to reduced DPTIF activity. Thus, it appeared that the core protein of DPTIF was PKR, and that PKR was maintained in an active state in stress granule aggregates with AHNAK and transported via microvesicles. The activity of DPTIF for TNF-α induction was far superior to that of gram-negative bacterial endotoxin. Therefore, we, report for the first time, that active PKR is transported via microvesicles as stress granule aggregates and induces powerful inflammatory signals in macrophages.
2018-12-30 | GSE124491 | GEO
Project description:It is well known that dental pulp tissue can evoke some of the most severe acute inflammation observed in the human body. We found that dental pulp cells secrete a factor that induces tumor necrosis factor-α production from macrophages, and designated this factor, dental pulp cell-derived tumor necrosis factor-α-inducing factor (DPTIF). DPTIF was induced in dental pulp cells and transported to recipient cells via microvesicles. Treatment of dental pulp cells with a PKR inhibitor markedly suppressed DPTIF activity, and weak interferon signals were constitutively activated inside the cells. In recipient macrophages, stimulation with DPTIF-containing supernatants from pulp cells resulted in activation of both nuclear factor-κB and MAP kinases like JNK and p38. Proteomics analyses revealed that many stress granule-related proteins were present in supernatants from dental pulp cells as well as microvesicle marker proteins like GAPDH, β-actin, HSPA8, HSPB1, HSPE1, and HSPD1. Furthermore, giant molecule AHNAK and PKR were detected in microvesicles derived from dental pulp cells, and gene silencing of AHNAK in pulp cells led to reduced DPTIF activity. Thus, it appeared that the core protein of DPTIF was PKR, and that PKR was maintained in an active state in stress granule aggregates with AHNAK and transported via microvesicles. The activity of DPTIF for TNF-α induction was far superior to that of gram-negative bacterial endotoxin. Therefore, we, report for the first time, that active PKR is transported via microvesicles as stress granule aggregates and induces powerful inflammatory signals in macrophages.
2018-12-30 | GSE124490 | GEO
Project description:Dental pulp cell-derived powerful inducer of TNF-alpha comprises PKR containing stress granule rich microvesicles (GFvsDP-1)
| PRJNA512200 | ENA
Project description: Not available
| S-EPMC6405945 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-12-30 | GSE124492 | GEO
Project description:Glioblastoma tumour cells release microvesicles (exosomes) containing mRNA, miRNA and angiogenic proteins. These microvesicles are taken up by normal host cells, such as brain microvascular endothelial cells. By incorporating an mRNA for a reporter protein into these microvesicles, we demonstrate that messages delivered by microvesicles are translated by recipient cells. These microvesicles are also enriched in angiogenic proteins and stimulate tubule formation by endothelial cells. Tumour-derived microvesicles therefore serve as a means of delivering genetic information and proteins to recipient cells in the tumour environment. Glioblastoma microvesicles also stimulated proliferation of a human glioma cell line, indicating a self-promoting aspect. Messenger RNA mutant/variants and miRNAs characteristic of gliomas could be detected in serum microvesicles of glioblastoma patients. The tumour-specific EGFRvIII was detected in serum microvesicles from 7 out of 25 glioblastoma patients. Thus, tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test.
2008-11-16 | GSE13470 | GEO
Project description:Global analysis of gene expression in NIH3T3 cells over-expressing RNA-dependent serine/threonine protein kinase (PKR). Keywords: other
2004-09-22 | GSE682 | GEO
Project description:Glioblastoma tumour cells release microvesicles (exosomes) containing mRNA, miRNA and angiogenic proteins. These microvesicles are taken up by normal host cells, such as brain microvascular endothelial cells. By incorporating an mRNA for a reporter protein into these microvesicles, we demonstrate that messages delivered by microvesicles are translated by recipient cells. These microvesicles are also enriched in angiogenic proteins and stimulate tubule formation by endothelial cells. Tumour-derived microvesicles therefore serve as a means of delivering genetic information and proteins to recipient cells in the tumour environment. Glioblastoma microvesicles also stimulated proliferation of a human glioma cell line, indicating a self-promoting aspect. Messenger RNA mutant/variants and miRNAs characteristic of gliomas could be detected in serum microvesicles of glioblastoma patients. The tumour-specific EGFRvIII was detected in serum microvesicles from 7 out of 25 glioblastoma patients. Thus, tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test. The glioblastoma cell and exosome RNA was analyzed on two dual color arrays.
2008-11-15 | E-GEOD-13470 | biostudies-arrayexpress
Project description:PKR (Protein Kinase RNA-activated) is activated by metabolic stress, such as that associated with obesity, and this activation depends on its RNA-binding domain. Here we investigated whether endogenous RNA triggers PKR activation in response to lipid exposure. Our results indicate that snoRNAs (small nucleolar RNAs) associate with PKR during metabolic stress. Our high-throughput sequence shows that snoRNAs are enriched in PKR_WT samples after palmitic acid treatment compared to mock-treated samples. MEF cells reconstituted with wild type PKR (PKR_WT) or PKR with a mutation in each dsRBM (PKR_RM) were mock- or palmitate-treated. RNAs associated with PKR were immunoprecipitated. IPed RNAs were extracted, cloned and sequenced. We performed differential expression to obtain RNAs enriched in PKRWT after palmitate treatment. We sequenced three different datasets of samples (A, B and C). Each A and B dataset contains three biological replicates. Dataset C contains a single sample.
2015-05-08 | E-GEOD-66540 | biostudies-arrayexpress