Transcriptional effects of catalytic mTOR inhibiton among LPS-stimulated primary human monocytes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA777550 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16761371.fastq.gz | Fastqsanger.gz | |||
| SRR16761372.fastq.gz | Fastqsanger.gz | |||
| SRR16761373.fastq.gz | Fastqsanger.gz | |||
| SRR16761374.fastq.gz | Fastqsanger.gz | |||
| SRR16761375.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
Similar Datasets
Project description:To better understand the role of mTOR in regulation of the monocyte response to LPS, we obtained mRNA-seq profiles of primary human monocytes stimulated ex vivo through TLR4, with and without pretreatment with a catalytic mTOR inhibitor (mTORi)
2022-07-29 | GSE187403 | GEO
Project description:To investigate the impact of mTOR inhibiton on TNFalpha-activated rheumatoid arthritis fibbroblast-like synoviocytes (RA-FLS)
2018-03-15 | E-MTAB-6457 | biostudies-arrayexpress
Project description:CD14+ Monocytes from healthy volunteers were purified by MACS (negative selection) and FACSorting and either left untreated or stimulated for 24h and 48h with LPS. THP-1 cells were stimulated for 4h, 24h and 48h with LPS. Glycoproteins were captured with hydrazide chemistry and tryptic and PNGase F-released peptide fractions analyzed by MS/MS. Quantitative assessment revealed differential glycoprotein expression in activated/LPS-tolerized monocytes and naïve monocytes and THP-1 cells.
2017-04-24 | PXD004034 | Pride
Project description:Sepsis is a severe and dysregulated inflammatory disease that often precedes the development of acute kidney injury (AKI) with consequent worsening outcome. The main characteristics of sepsis-induced AKI include endothelial cell (EC) dysfunction, infiltration of inflammatory cells, glomerular thrombosis, and renal tubular epithelial cells (RTEC) injury. Numerous studies have demonstrated that mammalian target of rapamycin (mTOR) activation has been implicated in the initiation and progression of renal injury in course of sepsis. However, little is known, about the molecular basis of mTOR role in EC and RTEC dysfunction. Here, we evaluate whether mTOR inhibition by Rapamycin (Rp) as potential strategy to ameliorate renal function and dissected the molecular mechanisms involved. In a mouse model of lipopolysaccharide (LPS)-induced AKI , LPS injection led to a time-dependent increase of serum creatinine and significant morphological changes in renal parenchyma associated with increased collagen deposits and endothelial dysfunction. Interestingly, Rp treatment significantly decreased creatine levels and preserved renal parenchyma, counteracting Endothelial-to mesenchymal transition (EndMT) process and early fibrosis through the inhibition of ERK pathway. Next, we examined the effects of LPS-TLR4 interaction in RTECs. Through a whole-genome DNA methylation analysis in cultured RTEC, we found that LPS induced aberrant methylation, particularly in regions involved in premature aging. The most represented genes were CD39 and WFS1. LPS stimulation of RTEC led to up-regulation of SA-β Gal and cell cycle arrest markers such as p21. In accordance, in endotoxemic mice, we found a decreased expression of CD39 concurrent with Klotho down-regulation. Administration of Rp exerted anti-aging effects in endotoxemic mice, preserving CD39 and Klotho expression. In conclusion, we demonstrated that mTOR inhibition could offer novel strategies to protect endothelial and tubular compartment from accelerated aging and fibrosis thus counteracting the progression to chronic kidney disease.
2024-09-16 | E-MTAB-13396 | biostudies-arrayexpress
Project description:Purpose: The purpose of this RNA-seq experiment was to perform a correlation analysis of mRNA expression levels in naïve CD4+ T cells and LPS-stimulated monocytes from patients with an IKZF1 mutant haploinsufficient phenotype (H167R-a and H167R-b are two siblings carrying IKZF1 p.H167R mutation) versus patients with an IKZF1 mutant dominant negative phenotype (C1, G1) along with five healthy normal controls (HC).
2018-04-05 | GSE112707 | GEO
Project description:Phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway activation contributes to mantle cell lymphoma (MCL) pathogenesis and drug resistance. However, the use of mTOR inhibitors as single agents have shown limited clinical efficacy in relation with drug activation of feedback loops. Selective PI3K inhibition or dual PI3K/mTOR catalytic inhibition are different therapeutic approaches developed to achieve effective pathway blockage. Here, we evaluated the antitumor activity of a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor in primary MCL cells. We found that dual PI3K/mTOR inhibitor modulated angiogenesis, tumor invasiveness and cytokine signaling compared to a mTOR inhibitor and a pan-PI3K inhibitor in MCL. We used microarrays to compare the effect of these three compounds in MCL and identified distinct classes of down-regulated genes modulated by each compound. Global RNA expression in primary cells from two MCL patients treated with a mTOR inhibitor, a pan-PI3K inhibitor and a dual PI3K/mTOR inhibitor for 8 hours
2013-12-14 | E-GEOD-53309 | biostudies-arrayexpress
Project description:H3K4me2 ChIP-seq upon GSK inhibiton
| PRJNA543247 | ENA
Project description:The TSC/mTOR (tuberous sclerosis complex/mammalian target of rapamycin) pathway has a central role in cell growth and is involved in human tumorigenesis. Here, we demonstrate an unexpected role of TSC2 and mTOR in regulating key inflammatory cytokines in monocytes, macrophages, and dendritic cells after bacterial stimulation. mTOR deficiency promoted IL-12/IL-23 and blocked IL-10 production via the transcription factor NF-kB. Conversely, loss of TSC2, a key negative regulator of mTOR, led to reduced NF-kB activity, limited IL-12 but enhanced IL-10 production. Transcriptional profiling demonstrated that mTOR additionally regulated many mediators important for inflammation and immunoregulation including PD-L1, CCR5, CCL22, and MCP-1. mTOR inhibition in vivo rescued susceptible mice from a lethal Listeria monocytogenes infection by modulating IL-12/IL-10 production. These data identify the TSC2/mTOR pathway as a novel pathway in innate immune responses by controlling NF-kB with profound clinical implications for infectious diseases, cancer, or transplantation. Keywords: inflammatory response of monocytes to LPS and rapamycin 107 CD14+ monocytes from four different donors were stimulated with 100 ng/ml LPS with or without 100 nM rapamycin for 4 hours. Cells were harvested, washed and pelleted and frozen at â80° C. Sample preparation and hybridization to a PIQORTM Immunology Microarray Human Antisense (quadrupled cDNA fragments for 1070 genes) was performed at the Miltenyi Microarray Service Unit. In brief, RNA was extracted with the TRIzol method (Sigma-Aldrich) and 1mg of total RNA was linear amplified by T7 polymerase. Total RNA from the LPS treated cells were Cy3 labeled, LPS and rapamycin treated cells were Cy5 labeled; both samples of a donor were hybridized on a single microarray. Only genes with signal intensities >2-fold above average background in one of the two channels were regarded as expressed.
2010-05-19 | E-GEOD-6002 | biostudies-arrayexpress
Project description:Purpose: The purpose of this study was to compare the BMDMs transcriptome in the control LPS and LPS plus BHB group in order to identify the critical pathway that contributed to the inhibiton of BHB on M1 polarization. Methods: 1× 106 BMDMs were pre-treated with PBS or BHB for 1 hours before LPS administration. Four hours later, BMDMs were harvested for RNA preparation. Results: Among 16650 mapped genes, 7325 differentially expressed genes were identified, including 244 LPS inducible BHB down regulated named class A and 537 LPS repressed BHB up regulated genes named class B. The genes in class A were mainly TLR4 and TNF signaling pathway, while genes in class B were associated with negative regulation of transcription and NF-KB signaling. The GSEA showed that BHB have the similar profiles chnage on BMDMs with TSA. Conclusions: Our study revealed that BHB down regulated TLR4 and NF-KB pathway related genes to inhibited M1 polarization, and BHB have a similar effect on BMDMs with TSA through comparing the genetic changes of two substance caused in cells.
2022-04-06 | GSE152241 | GEO