Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effects of HIV protein Tat on macrophage transcriptome

ABSTRACT: Purpose: To investigate the impact of HIV protein Tat on macrophage transcriptome related to atherosclerosis development Methods: Peritoneal macrophages were isolated from myeloid specific IKKβ deficient LDLR-/- (IKKβΔMyeLDLR-/-) mice and their littermates (IKKβF/FLDLR-/-). Then the macrophages were treated with HIV protein Tat or control for 12 hr. Total RNA was extracted for RNAseq Results: HIV protein Tat treatment induces 2640 differentially expressed genes (DEGs) with false discovery rate (FDR) < 1 % and fold change > 3 in control macrophages. Those DEGs enriched in several biological processes that may contribute to atherogenesis. FAIME analysis demonstrated higher geneset scores of those GO terms in the Tat-treated macrophages from IKKβF/FLDLR-/- mice compared with the control ones. IKKβ deletion resulted in loss of geneset score in the macrophages of IKKβΔMyeLDLR-/- treated with HIV Tat. Conclusions: These results indicate that HIV protein Tat may affect many genes in macrophages related atherosclerosis development through IKKβ signaling.

ORGANISM(S): Mus musculus

PROVIDER: GSE157833 | GEO | 2021/07/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The impact of Spike protein on macrophage inflammation

Project description:Purpose: To elucidate how SARS-CoV-2 spike protein affects macrophage inflammatory responses Methods: Peritoneal macrophages were isolated from Myeloid-specific IKKβ knockout mice (IKKβΔMye) and control littermates (IKKβ F/F). Then the macrophages were treated with lentivirus expressing Spike protein for 24 hours Results: Deficiency of IKKβ nearly abolished spike protein-associated geneset scores and DEGs-associated key inflammatory pathways. Conclusions: These results indicate that SARS-CoV-2 Spike protein induces strong inflammatory responses in macrophages, potentially through activation of canonical IKKβ/NF-κB signaling

2022-04-06 | GSE182264 | GEO

Macrophage DCLK1 promotes atherosclerosis via binding to IKKβ and inducing inflammatory responses

Project description:Atherosclerosis is a chronic inflammatory disease with high morbidity and mortality rates worldwide. Doublecortin-like kinase 1 (DCLK1), a microtubule-associated protein kinase, is involved in neurogenesis and human cancers. However, the role of DCLK1 in atherosclerosis remains undefined. In this study, we identified up-regulated DCLK1 in macrophages in atherosclerotic lesions of ApoE-/- mice fed an HFD and determined that macrophage-specific DCLK1 deletion attenuates atherosclerosis by reducing inflammation in mice. Mechanistically, RNA sequencing analysis indicated that DCLK1 mediates oxLDL-induced inflammation via NF-κB signaling pathway in primary macrophages. Co-immunoprecipitation followed by LC-MS/MS analysis identified IKKβ as a binding protein of DCLK1. We confirmed that DCLK1 directly interacts with IKKβ and phosphorylates IKKβ at S177/181, thereby facilitating subsequent NF-κB activation and inflammatory gene expression in macrophages. Finally, a pharmacological inhibitor of DCLK1 prevents atherosclerotic progression and inflammation both in vitro and in vivo. Our findings demonstrated that macrophage DCLK1 promotes inflammatory atherosclerosis by binding to IKKβ and activating IKKβ/NF-κB. This study reports DCLK1 as a new IKKβ regulator in inflammation and a potential therapeutic target for inflammatory atherosclerosis.

2023-02-27 | PXD039083 | Pride

Macrophage DCLK1 promotes atherosclerosis via binding to IKKβ and inducing inflammatory responses

2022-12-24 | GSE221647 | GEO

Expression data from human antigen presenting cells expressing HIV-1 Tat alleles and mutants

Project description:HIV-1 Tat induces the expression of interferon (IFN)-inducible genes in immature dendritic cells (iDC) in the absence of IFN production. We evaluated how three alleles of Tat and some Tat mutants differ in cellular gene modulation and whether a similar gene induction pattern could be detected by treating cells with IFNM-bM-^@M-^Ys. The three alleles and mutants, with the exception of mutants TatSF21-47 and TatSF2G48-R57A that do not localize in the nucleous, modulated to different degrees IFN-inducible genes without concomitant induction of IFNM-bM-^@M-^Ys. The first exon TatSF21-72 and the minimal transactivator TatSF21-58, all induced genes to a significantly greater extent than full-length Tat. The 2nd exon appears to diminish the gene modulation that can be observed when the first exon alone is expressed. To investigate what domain of Tat are critical to the host-pathogen interactions that are Tat-dependent during HIV infection, we evaluated a variety of Tat-mutants and found that in antigen presenting cells, blood-derived myeloid iDC and macrophages, the second exon of Tat reduces innate immunological responses which are maximal when a Single exon Tat is expressed. 1X10e6 macrophages were infected with HIVBal (20 ng of p24/ 106 cells) for 10 days and with adenoviruses expressing TatHXB2 or LacZ control (5 pfu per cell). Cells infected with Ad-Tat or Ad-LacZ were collected at 24 hours and cells infected with HIV or treated with medium were harvested at 7d and 10d post-infection. THP-Mac were infected with Ad-Tat or Ad-tTA control for 24 hours. RNA was isolated and mRNA expression levels were analyzed by microarrays. adenovirus expressing HIV Tat for 30 hours. and then RNA was isolated, labeled, and prepared for hybridization on Affymetrix microarrays.

2013-06-01 | E-GEOD-42925 | biostudies-arrayexpress

ChIP-chip from KG-1 cells with HIV Tat

Project description:HIV-1 Tat can modulate the expression of both HIV and cellular genes. In antigen-presenting cells Tat induces the expression of a subset of interferon-stimulated genes (ISGs) in the absence of interferons (IFNs). We investigated the genome-wide Tat association with cellular promoters in immature dendritic cells (iDC) and in monocyte derived macrophages (MDM). Chromatin immunoprecipitation (ChIP) of Tat together with chromatin profiling by ChIP-on-chip analysis demonstrated that Tat associates with the MAP2K6 and MAP2K3 promoters and mediates its increase, which also affects the induction of some ISGs. comparison of KG-1 cells expressing tTA control vs Tat or mutant TatSF2G48R57A

2013-05-31 | E-GEOD-42191 | biostudies-arrayexpress

Discovery of Dual targeting PEGylated BG-P1600-TAT to Norepinephrin Transporter (NET) and Thyrointegrin αvβ3 in the Treatment of Neuroblastoma cancer cellline

Project description:Molecular mechanisms of anti-cancer activities of BG-P1600-TAT were explored employing genome-wide expression profiling experiments. Human neuroblastoma cell line SK-N-FI and primary cells SKNAS were treated with 30µM of the BG-P1600-TAT for 48 hours, harvested, and total RNA was immediately isolated from three biological replicates of control (vehicle-treated) and BG-P1600-TAT-treated cells. Gene expression profiling experiments identified 14-gene BG-P1600-TAT molecular interference signature captured most biologically important significantly enriched records reflecting the putative molecular mechanisms of anti-cancer activities of the BG-P1600-TAT. In BG-P1600-TAT treated SK-N-FI cells, 753 differentially expressed genes (DEGs) were identified compared to control vehicle-treated cells. Among 753 DEGs, 427 genes were down-regulated and 326 genes were up-regulated. In SKNAS cells, BG-P1600-TAT showed a significant effects on signal transduction pathways activated during cellular responses to IL-1alpha, TNF-alpha, EGF, TGF, PDGF, and AR. Further BG-P1600-TAT also showed a significant effect on multiprotein complexes of potential biological and therapeutic significance, including several complexes engaged during apoptosis (BCL-2 family protein complex; Survivin complex; BAX complex; Caspase complex), angiogenesis (VEGF-A complex; Thrombospondin complex), and cell adhesion (Galectin complex; Integrin alpha/beta complexes).

2021-09-06 | GSE183482 | GEO

The RNA-binding proteins SRP14 and HMGB3 control HIV-1 Tat mRNA processing and translation during HIV-1 latency

Project description:HIV-1 Tat protein is essential for virus production. RNA-binding proteins that facilitate Tat production may be absent or downregulated in resting CD4+ T-cells, the main reservoir of latent HIV. In this study, we examined the role of Tat RNA-binding proteins on the expression of Tat and control of latent and productive infection.

2021-06-14 | PXD025782 | Pride

HIV-1 Tat and Methamphetamine interaction in the mouse brain

Project description:Our goal was to examine whether the HIV Tat peptide, which is usually secreted from infected cells and has the potential to act in other cell types, alters gene expression in the Central Nervous System, and whether a drug abuse co-morbidity, in the case Methamphetamine, can play a role in further modifying gene expression. In order to address the effects of HIV Tat and Methamphetamine, alone and combined, we used an in vivo mouse model that has been described to mimic several aspects of neuroHIV, including changes in inflammatory markers, and decreased expression of dopamine receptors. These animals are transgenic mice, which upon treatment with with doxycycline for 10 days, express TAT protein under the control of the glial fibrilary associated protein (GFAP) promoter in the brain. They were treated with Meth and Saline for identification of gene expression changes that result from Tat or Methamphetamine alone, or from their interaction. There was an overall suppression of gene expression by Methamphetamine, in Tat- mice. The expression of Tat caused most Meth-induced changes to remain at control levels.

2018-03-17 | GSE111925 | GEO

HIV-1 Tat protein promotes neuronal dysfunction through disruption of microRNAs

Project description:Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release from the infected cells and taken up by noninfected cells. Using microRNA array assay, we demonstrated that Tat deregulates the levels of several miRNAs. Interestingly, miR-34a was among the most highly induced miRNAs in Tat-treated neurons. Tat also decreases the levels of miR-34a target genes such as CREB protein as shown by real time PCR. The effect of Tat was neutralized in the presence of anti-miR-34a. Using in situ hybridization assay, we found that the levels of miR-34a increase in Tat transgenic mice when compared with the parental mice. Therefore, we conclude that deregulation of neuronal functions by HIV-1 Tat protein is miRNA-dependent. Human fetal neurons were chosen to examine the impact of HIV-1 Tat protein on gene expression

2012-12-07 | E-GEOD-42423 | biostudies-arrayexpress

HIV-1 Tat protein promotes neuronal dysfunction through disruption of microRNAs [differentiated SH-5Y cells]

Project description:Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release from the infected cells and taken up by noninfected cells. Using microRNA array assay, we demonstrated that Tat deregulates the levels of several miRNAs. Interestingly, miR-34a was among the most highly induced miRNAs in Tat-treated neurons. Tat also decreases the levels of miR-34a target genes such as CREB protein as shown by real time PCR. The effect of Tat was neutralized in the presence of anti-miR-34a. Using in situ hybridization assay, we found that the levels of miR-34a increase in Tat transgenic mice when compared with the parental mice. Therefore, we conclude that deregulation of neuronal functions by HIV-1 Tat protein is miRNA-dependent. Human neurons SH-SY5Y were chosen to examine the impact of HIV-1 Tat protein on gene expression

2013-01-17 | E-GEOD-43534 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data