TNFα secreted from macrophages increases expression of prometastatic integrin αV in gastric cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA910141 | ENA |
REPOSITORIES: ENA
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Project description:We performed RNA-Seq to confirm the changes in expression of genes in the relevant pathway in human gastric cancer cells (AGS cells) and AGS cells cocultured with macrophages (RAW264.7 cells). In the gene ontology enrichment analysis of the 160 genes that were increased in AGS cells cocultured with RAW264.7 cells, pathways related to immune response, cell adhesion, and cytokine response were enriched.
2022-12-12 | GSE220531 | GEO
Project description:Background: Herbicides are environmental contaminants that have gained much attention due to the potential hazards they pose to human health. Glyphosate, the active ingredient in many commercial herbicides, is the most heavily applied herbicide worldwide. The recent rise in glyphosate application to corn and soy crops correlates positively with increased death rates due to Alzheimer's disease and other neurodegenerative disorders. Glyphosate has been shown to cross the blood-brain barrier in in vitro models, but has yet to be verified in vivo. Additionally, reports have shown that glyphosate exposure increases pro-inflammatory cytokines in blood plasma, particularly TNFα. Methods: Here, we examined whether glyphosate infiltrates the brain and elevates TNFα levels in 4-month-old C57BL/6J mice. Mice received either 125, 250, or 500 mg/kg/day of glyphosate, or a vehicle via oral gavage for 14 days. Urine, plasma, and brain samples were collected on the final day of dosing for analysis via UPLC-MS and ELISAs. Primary cortical neurons were derived from amyloidogenic APP/PS1 pups to evaluate in vitro changes in Aβ40-42 burden and cytotoxicity. RNA sequencing was performed on C57BL/6J brain samples to determine changes in the transcriptome. Results: Our analysis revealed that glyphosate infiltrated the brain in a dose-dependent manner and upregulated TNFα in both plasma and brain tissue post-exposure. Notably, glyphosate measures correlated positively with TNFα levels. Glyphosate exposure in APP/PS1 primary cortical neurons increases levels of soluble Aβ40-42 and cytotoxicity. RNAseq revealed over 200 differentially expressed genes in a dose-dependent manner and cell-type-specific deconvolution analysis showed enrichment of key biological processes in oligodendrocytes including myelination, axon ensheathment, glial cell development, and oligodendrocyte development. Conclusions: Collectively, these results show for the first time that glyphosate infiltrates the brain, elevates both the expression of TNFα and soluble Aβ, and disrupts the transcriptome in a dose-dependent manner, suggesting that exposure to this herbicide may have detrimental outcomes regarding the health of the general population.
2024-01-15 | GSE253299 | GEO
Project description:Control, TNFα and TNFα+JNK I treated GSCs
| PRJNA799754 | ENA
Project description:Glyphosate infiltrates the brain and increases pro-inflammatory cytokine TNFα: implications for neurodegenerative disorders
| PRJNA1064995 | ENA
Project description:Mouse intestinal epithelial cells (IEC4.1 cells) were stimulated with TNFα (10 ng/ml) for 4h. The Agilent SurePrint G3 Mouse Gene Expression Microarray (G4852A) was used for the analysis, which provides full coverage of genes and transcripts with the most up-to-date content, including mRNAs and lincRNAs (http://www.chem.agilent.com/store/en_US/Prod-G4852A/G4852A). IEC4.1 cells were grown to 80% confluence for four groups: the siRNA control (Group A, cells treated with a non-specific scrambied siRNA control), the TNFα -stimulated (Group B, cells treated with the siRNA control plus TNFα stimulation), lincRNA-Cox2 siRNA (Group C, cells treated with an siRNA to lincRNA-Cox2), and lincRNA-Cox2 siRNA/ TNFα stimulated (Group D, cells treated with the lincNRA-Cox2 siRNA plus TNFα stimulation). Cells were treated with the siRNAs for 24h, followed by additional culture for 4h in the presence or absence of TNFα (10 ng/ml). Total RNAs were prepared with the RNeasy Mini kit (Qiagen) according to the manufacturer’s instruction (Ambion).
2016-10-25 | E-MTAB-3904 | biostudies-arrayexpress
Project description:Cellular senescence is a key cell-fate program that leads to an essentially irreversible proliferative arrest in potentially damaged cells. Cytokine production and signaling play a significant role in senescence. Tumor necrosis factor-alpha (TNFα), an important pro-inflammatory cytokine secreted by some senescent cells, can induce senescence in mouse and human cells. However, downstream signaling pathways and key regulatory genes linking inflammation to senescence are not fully characterized. Using human umbilical vein endothelial cells (HUVECs) as a model, we show TNFα induces permanent growth arrest and increased senescence markers such as p21, p16, and senescence-associated β-galactosidase (SA-β-gal), accompanied by persistent DNA damage and ROS. By gene expression profiling and pathway analysis, we identify the crucial involvement of inflammatory networks, an interferon signature, and persistent activation of the Janus kinase (JAK) /signal transducer and activator of transcription (STAT) pathway in TNFα-mediated senescence. TNFα initiates a STAT-dependent autocrine loop leading to sustained inflammation, DNA damage, and expression of interferon response genes to lock cells into senescence. Further, we show STAT1/3 activation is necessary for cytokine and ROS production during TNFα-induced senescence. However, inhibition of STAT1/3 did not rescue cells from TNFα-mediated senescence. Rather, blockade of STAT activation accelerated senescence, suppressed genes that control the cell cycle, and modulated TNFα-induced senescence. Our findings suggest a positive feedback mechanism via a STAT pathway that sustains cytokine production and reveal a reciprocal regulatory role of JAK/STAT in TNFα-mediated senescence.
2017-04-24 | GSE98081 | GEO
Project description:Among 830 TNFα-induced genes (at least 1.5 folds of upregulation in TNFα-treated TPC2-4 cells compared with control), the expression of 268 genes is significantly suppressed by JNKi treatment (TPC2-4 TNFα+JNKi/TPC2-4 TNFα, JNKi: JNK-IN-8, a kinase inhibitor specific for JNK (c-Jun N-terminal kinase) that inhibited phosphorylation of c-JUN)
2022-08-24 | GSE194220 | GEO
Project description:Cellular senescence is a key cell-fate program that leads to an essentially irreversible proliferative arrest in potentially damaged cells. Cytokine production and signaling play a significant role in senescence. Tumor necrosis factor-alpha (TNFα), an important pro-inflammatory cytokine secreted by some senescent cells, can induce senescence in mouse and human cells. However, downstream signaling pathways and key regulatory genes linking inflammation to senescence are not fully characterized. Using human umbilical vein endothelial cells (HUVECs) as a model, we show TNFα induces permanent growth arrest and increased senescence markers such as p21, p16, and senescence-associated β-galactosidase (SA-β-gal), accompanied by persistent DNA damage and ROS. By gene expression profiling and pathway analysis, we identify the crucial involvement of inflammatory networks, an interferon signature, and persistent activation of the Janus kinase (JAK) /signal transducer and activator of transcription (STAT) pathway in TNFα-mediated senescence. TNFα initiates a STAT-dependent autocrine loop leading to sustained inflammation, DNA damage, and expression of interferon response genes to lock cells into senescence. Further, we show STAT1/3 activation is necessary for cytokine and ROS production during TNFα-induced senescence. However, inhibition of STAT1/3 did not rescue cells from TNFα-mediated senescence. Rather, blockade of STAT activation accelerated senescence, suppressed genes that control the cell cycle, and modulated TNFα-induced senescence. Our findings suggest a positive feedback mechanism via a STAT pathway that sustains cytokine production and reveal a reciprocal regulatory role of JAK/STAT in TNFα-mediated senescence.
2017-03-10 | GSE92655 | GEO
Project description:Among 3,673 TNFα-induced gain of accessibility (at least 2 folds of upregulation in TNFα-treated TPC2-4 cells compared with control), and most of the gained peaks were significantly suppressed by JNKi treatment (TPC2-4 TNFα+JNKi/TPC2-4 TNFα, JNKi: JNK-IN-8, a kinase inhibitor specific for JNK (c-Jun N-terminal kinase) that inhibited phosphorylation of c-JUN)
2022-08-24 | GSE194221 | GEO
Project description:TNFα is a cytokine with multiple biological effects. It activates cascading signal pathways by binding to receptors on the cell membrane, regulating processes such as cell growth, differentiation, apoptosis, and inflammatory responses. The formation of skeletal muscle primarily relies on processes such as myoblasts proliferation, migration, differentiation, cytoskeletal rearrangement, and myotube fusion, which constitute a complex and coordinated process regulated by multiple genes. While research on TNFα has primarily focused on immunology, some studies suggest that TNFα also plays a physiological role in myogenesis, muscle repair, diseases, and atrophy.We isolated the nuclei (N) and cytoplasm (C) of flox and TNFα-CKO primary myoblasts in the early stages of differentiation and attempted to identify new targets in the TNFα signaling pathway.
2024-08-09 | PXD046525 | Pride