Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effects of imiquimod on macrophages by transcriptomic analysis

ABSTRACT: Imiquimod is a small-molecule immunomodulator with anti-tumor effects, and its anti-tumor activity mainly relies on its immunomodulatory capacity, including activating dendritic cells， T cells, natural killer cells, and promoting the migration of antigen-presenting cells. In this study, we pretreated mouse bone marrow-derived macrophages (BMDMs) with imiquimod for 24 hours and conducted transcriptomic analysis to explore the mechanism by which imiquimod regulates macrophages to exert anti-tumor effects. We found that imiquimod pretreatment of macrophages upregulated multiple signaling pathways, with the most significant being immune regulation-related signaling pathways. Notably, pathways such as the NF-κB pathway, Toll-like receptor (TLR) pathway were significantly upregulated. We infer that imiquimod activates TLR pathway and the downstream NF-κB pathway, promoting the polarization of macrophages to a pro-inflammatory phenotype and exerting anti-tumor effects.

ORGANISM(S): Mus musculus

PROVIDER: GSE305492 | GEO | 2025/08/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

TLR4-NFkB-phospho-NF-kB signaling in BMDM

Project description:The model was constructed to describe TLR4 induced NF-κB activation in native bone marrow-derived macrophages. It included processes of ligand (lipopolysaccharide) recognition, formation of dimer receptor complex and further signal transduction through TRAF6/TAK1 complex that leads to the activation of IKKα/β kinase, which in turn enables the NF-κB transcription factor phosphorylation and translocation in the cell nucleus, and induction of IkB and WIP1 (as an example of induced protein that promotes NF-κB dephosphorylation 2) gene transcription. Models were based on the current knowledge of TLR signaling framework, protein interactions within the TLR4 pathway, and up-to-date mathematical models describing Toll receptor activation. The major important additions were made to TLR4 signaling description: 1) Receptor dimerization process 2) The existence of a basal nuclear NF-κB level (translocation) 3) NF-κB phosphorylation by IKK complex

2019-03-27 | MODEL1809230001 | BioModels

The protection of Evodiamine against Ulcerative Colitis and Colorectal Cancer via anti-inflammation

Project description:Evodiamine (Evo), a kind of alkaloid mostly extracted from Tetradium ruticarpum, which has many pharmacological functions, such as antidiarrheal, antiemetic, and antiulcer effects. In this study, the effects of Evo were investigated in DSS-induced ulcerative colitis (UC) mice and C57BL/6-ApcMinC/Gpt mice with colorectal cancer (CRC). The results showed Evo not only sup-pressed the weight loss and the shorthen of colon, decreased disease activity index (DAI) and ameliorated the pathological alteration of colon in UC mice, but also inhibited the numbers and sizes of colonic tumor of ApcMinC/Gpt mice. Meanwhiles, Evo regulated nuclear factor-kappa B (NF-κB) related signal pathways to mediate various cytokines such as interleukins (Ils), tumor necrosis factor-α (TNF-α) to achieve anti-inflammatory and anti-tumor effects. In SW480 and Caco cells, Evo reduced the cell viabilities, promoted the mitochondrial membrane potential (MMP) and caused the over-accumulation of intracellular reactive oxygen species (ROS). Theoretical evi-dences indicated Evo binding NF-κB may be useful to contain ordered domain (α helix) in NF-κB, which can induce NF-κB to perform its function. Our results provide experimental and theoretical evidence that Evo might be promising and effective treatments in clinics for UC and CRC.

2022-05-20 | PXD027745 | Pride

Noncanonical pathway for regulation of CCL2 expression by an mTORC1-FOXK1 axis promotes recruitment of tumor-associated macrophages

Project description:C-C chemokine ligand 2 (CCL2) plays pivotal roles in tumor formation, progression, and metastasis. Although CCL2 expression has been found to be dependent on the nuclear factor (NF)–κB signaling pathway, the regulation of CCL2 production in tumor cells has remained unclear. Mammalian target of rapamycin complex 1 (mTORC1) is a protein kinase that is activated in various tumor cell types. We have now identified a noncanonical pathway for regulation of CCL2 production that is mediated by mTORC1 but independent of NF-κB. Multiple phosphoproteomics approaches identified the transcription factor forkhead box K1 (FOXK1) as a downstream target of mTORC1, with dephosphorylation of FOXK1 in response to mTORC1 activation resulting in transactivation of the CCL2 gene. Inhibition of the mTORC1-FOXK1 axis attenuated insulin-induced CCL2 production as well as the accumulation of tumor-associated monocytes-macrophages and tumor progression in mice. Our results suggest that FOXK1 directly links mTORC1 signaling and CCL2 expression in a manner independent of NF-κB, and that CCL2 produced by this pathway contributes to tumor progression. Specific inhibition of FOXK1 may thus be a potential therapeutic strategy for cancer.

2017-11-30 | PXD007996 | Pride

Gene expression of macrophages treated with hY3

Project description:Based on the consistent demonstration of fibrosis of the atrioventricular node surrounded by macrophages and multinucleated giant cells in anti-Ro antibody exposed fetuses dying with heart block, this study focuses on macrophage signaling stimulated by ssRNA associated with the Ro60 protein and the impact of antagonizing innate cell drivers such as TLR7/8. Transcriptome and epigenetic modifications which affect transcription factors, NF-κB and STAT1, were selected to evaluate the phenotype of macrophages in which TLR7/8 was ligated following treatment with either anti-Ro60/Ro60/hY3 RNA immune complexes or transfection with hY3. Based on microarray, TNF and IL6 were among the most highly upregulated genes in both stimulated conditions, each of which was significantly inhibited by preincubation with hydroxychloroquine (HCQ). In contrast, following stimulation of macrophages with either TNF-α or IFN-α, which do not signal through TLR, the resultant gene expression was refractory to HCQ. Ligation of TLR7/8 resulted in increased histone methylation as measured by increased H3K4me2, a requirement for binding of NF-κB at certain promoters, specifically the kB1 region in the TNF promoter (ChIP-qPCR), which was significantly decreased by HCQ. In summary, these results support that the HCQ-sensitive phenotype of hY3 stimulated macrophages reflects the bifurcation of TLR downstream signals involving NF-κB and STAT 1 pathways and for the former dimethylation of H3K4. Accordingly, HCQ may act more as a preventive measure in downregulating the initial production of IFN-α or TNF-α and not affect the resultant autocoid stimulation reflected in TNF-α and IFN-α responsive genes. The beneficial scope of antimalarials in the prevention of organ damage, inclusive of heart block in an anti-Ro offspring or more broadly SLE, may include in part, a mechanism targeting TLR-dependent epigenetic modification.

2018-10-24 | GSE121704 | GEO

Novel spirocyclic dimer, SpiD3, targets critical tumor survival pathways and displays potent preclinical activity in B-cell chronic lymphocytic leukemia

Project description:Chronic lymphocytic leukemia (CLL) cell survival and growth is fueled by aberrant activation of various pro-survival signaling pathways within tumor niches. Specifically, B-cell receptor (BCR) signaling, toll-like receptor signaling, and supportive cellular interactions drive constitutive activation of NF-κB signaling and transcription of proliferative/pro-survival genes. Directly targeting the NF-κB pathway has been a challenge, however, herein, we investigated SpiD3, a spirocyclic dimer and novel NF-κB pathway inhibitor in preclinical models of CLL. Through cross-linking NF-κB proteins, SpiD3 attenuated NF-κB signaling in CLL cells independent of microenvironmental signals. Our integrated multi-omics and functional analyses revealed BCRNF-κB signaling, endoplasmic reticulum stress, oxidative stress, and activation of the unfolded protein response among the top pathways modulated by SpiD3 treatment. This was accompanied by marked inhibition of global protein synthesis, cumulating in profound anti-tumor properties in CLL cells. SpiD3 also modulated tumor microenvironment interactions shown by decreased chemokine and cytokine gene expression as well as decreased CLL chemotaxis towards CXCL-12 and CXCL-13. Moreover, SpiD3 induced apoptosis of stroma-protected primary CLL cells comparable to the BCR-targeting agent, ibrutinib. SpiD3 strikingly demonstrated selective cytotoxicity towards CLL cells compared to healthy lymphocytes, synergized with ibrutinib, and retained its anti-tumor effects in ibrutinib-resistant CLL cells. Altogether, our findings provide preclinical evidence for SpiD3 as an attractive therapeutic agent for CLL, especially in the context of relapsed/refractory disease.

2024-04-26 | GSE236239 | GEO

Gene expression data from HEK-293T cells transfected with miR-194 mimics

Project description:Nuclear factor κB (NF-κB) pathway plays an important role in hepatocellular carcinoma (HCC) progression. miR-194 was previously shown to reduce the induction of NF-κB activity upon addition of tumor necrosis factor α (TNFα). To clarify the molecular mechanism responsible for the effect of miR-194 on NF-κB pathway, mRNA microarray assays were performed to identify the genes that were suppressed by miR-194. HEK-293T cells transfected with miR-194 mimics were cultured for RNA extraction and hybridization on Affymetrix mRNA microarrays. These were compared against the control, which were HEK-293T cells transfected with negative control mimics.

2015-07-01 | E-GEOD-70434 | biostudies-arrayexpress

Surufatinib increases cholangiocarcinoma cells radiosensitivity by anti-tumor proliferation and inhibition of macrophage M2 polarization

Project description:This study confirmed the radiosensitizing effects of surufatinib on cholangiocarcinoma. The mechanism is that surufatinib can activate TLR3, up-regulate the expression of TRIF protein, increase DNA damage and apoptosis after radiation, and up-regulate NF- κB signal pathway to inhibit M2 polarization of tumor-associated macrophages, thus enhance radiosensitivity.

2024-06-30 | GSE269494 | GEO

Anti-inflammatory effects of differential molecular weight hyaluronic acids on UVB-induced calprotectin-mediated keratinocyte inflammation

Project description:Background: The biological functions of HA are related to its molecular weight and binding to its receptor TLR4 or CD44. Recent studies have shown that LMW-HA exhibits proinflammatory effects, while HMW-HA functions as an anti-inflammatory factor. UVB-induced epidermal inflammation is mainly mediated by endogenous molecules, such as DAMPs, that cause severe skin damage by activating TLR signaling pathways. Objective: Since both LMW- and HMW-HA have inhibitory functions on TLR-mediated macrophage inflammation, HA is assumed to suppress UVB-induced DAMP-mediated inflammation in the skin. In this study, both uLMW-HA and HMW-HA were found to inhibit UVB-induced keratinocyte inflammation. Methods: To elucidate whether HAs have anti-inflammatory effects on inflammation induced by UVB exposure, we performed whole transcriptome analysis in HaCaT cells treated with or without HAs after UVB exposure. Results: UV radiation induced upregulation or downregulation of genes (FC>1.2 or FC<0.8, q<0.05) were obtained. We analyzed network of these genes with Ingenuity Pathway analysis using information collected from databases on protein interactions. IL-6 was detected as an upstream factor of HA suppressing UV-radiation effects on HaCaT cells. Canonical pathway analysis also shows uLMW-HA downregulated NF-κB, which is located downstream of TLR4 signaling pathway, although HMW-HA did not show downregulation of NF-κB signaling pathway. Conclusions: Both uLMW-HA and HMW-HA were found to inhibit UVB-induced keratinocyte inflammation.

2022-08-05 | GSE201850 | GEO

TPPU alleviate cartilage degradation in temporomandibular joint osteoarthritis by inhibiting M1 macrophage polarization through the EETs/IL-17/NF-KB signaling pathway

Project description:In the treatment of inflammatory diseases, TPPU has shown potential therapeutic effects on a variety of inflammatory conditions, including reshaping the body's pro-inflammatory/anti-inflammatory balance by stabilizing endogenous anti-inflammatory substances EETs. In cardiovascular diseases, TPPU can regulate the NF-κB signaling pathway to modulate macrophage polarization and reduce inflammation. To explore the mechanism of TPPU in regulating M1 macrophages in TMJOA, we treated M1 macrophages with TPPU. In short, we attempted to verify the key signaling molecules and pathways regulated by TPPU in M1 macrophages.

2025-01-01 | GSE285011 | GEO

Expression data comparing the effect of IKK2 KO on a KRAS mouse model

Project description:Given that the NF-κB pathway plays an important role in tumor development and that IKK2 is the seminal kinase responsible for NF-κB pathway activation, we were particularly interested in exploring the therapeutic potential of IKK2 inhibition in non-small cell lung cancers. We crossed IKK2fl/fl and KrasG12D mice so that we could simultaneously activate KrasG12D to initiate tumor formation and inactivate IKK2, upon transduction by Cre lentiviral vectors. RNA isolated from finely dissected tumor nodules and tumor cell lines (4A3 and1D3) was applied to microarray analysis using Affymetrix Mouse Gene 1.0 STArrays according to the manufacturer’s instructions.

2011-12-15 | E-GEOD-30049 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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