TNF-α induces IL-32 expression in HEK293 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE121361 | GEO | 2019/02/28
REPOSITORIES: GEO
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Project description:TNF-α induces IL-32 expression in HEK293 cells
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Project description:PurposeRetinopathies display complex pathologies, including vasculopathies, inflammation, and fibrosis, leading ultimately to visual impairment. However, animal models accurately reflecting these pathologies are lacking. In this study, we evaluate the suitability of using Adeno-associated virus (AAV)-mediated long-term expression of cytokines to establish retinal pathology in the murine retina.MethodsWe administered recombinant, Müller-glia targeted AAV-ShH10 into the mouse vitreous to induce retinal expression of either human vascular endothelial growth factor (VEGF)-A165, tumor necrosis factor alpha (TNF-α), or interleukin-6 (IL-6) and evaluated consequent effects by optical coherence tomography, fluorescein angiography, and histology.ResultsIntravitreal injection of AAVs resulted in rapid and stable expression of the transgenes within 1 to 6 weeks. Akin to the role of VEGF-A in wet age-related macular degeneration, expression of VEGF-A led to several vasculopathies in mice, including neovascularization and vascular leakage. In contrast, the expression of the proinflammatory cytokines TNF-α or IL-6 induced retinal inflammation, as indicated by microglial activation. Furthermore, the expression of TNF-α, but not of IL-6, induced immune cell infiltration into the vitreous as well as vasculitis, and subsequently induced the development of fibrosis and epiretinal membranes.ConclusionsIn summary, the long-term expression of human VEGF-A165, TNF-α, or IL-6 in the mouse eye induced specific pathologies within 6 weeks that mimic different aspects of human retinopathies.Translational relevanceAAV-mediated expression of human genes in mice is an attractive approach to provide valuable insights into the underlying molecular mechanisms causing retinopathies and is easily adaptable to other genes and preclinical species supporting drug discovery for retinal diseases.
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Project description:TNF alpha is one of the inflammatory mediator and induce genes mainly by transcriptional factor, p65, in endothelial cells. This time, we performed a time course study to detect the change of localization of p65 and Pol II. To identify p65 and Pol II binding sites, we used chromatin immunoprecipitation with deep sequencing (ChIP-seq) of HUVECs treated with or without TNF alpha for 30 mins. Cells were starved before stimulation longer than 16 hours. HUVECs were used within the first 6 passages. For crosslinking, 10 mM of EGS in 50% glacial acetic acid was used for 45 min, followed by 20 min of 1% paraformaldehyde treatmet was used.
2013-01-01 | E-GEOD-34500 | biostudies-arrayexpress
Project description:In fibroblasts, p65-dependent genes can be sub-divided, depending on whether they are Trap-80-dependent or -independent. To examine the generality of this grouping, we performed a microarray analysis of wild-type and Trap-80 knock-down fibroblasts, before and after stimulation of NF-kappaB activity using TNF-alpha.
2009-04-01 | GSE12697 | GEO
Project description:In fibroblasts, p65-dependent genes can be sub-divided, depending on whether they are Trap-80-dependent or -independent. To examine the generality of this grouping, we performed a microarray analysis of wild-type and Trap-80 knock-down fibroblasts, before and after stimulation of NF-kappaB activity using TNF-alpha. RNA was extracted from three independent cultures of wild-type and Trap-80 knock-down fibroblasts, before and after stimulation for 1 hour with 5ng/ml TNF-alpha. The unstimulated and stimulated wild-type samples, and the stimulated Trap-80 knock-down samples, were used for microarray analysis.
2010-04-09 | E-GEOD-12697 | biostudies-arrayexpress
Project description:TNF alpha is one of the inflammatory mediator and induce genes mainly by transcriptional factor, p65, in endothelial cells. This time, we performed a time course study to detect the change of localization of p65 and Pol II.
2013-01-01 | GSE34500 | GEO
Project description:The mucosal barrier in combination with innate immune system are the first line of defense against luminal bacteria at the intestinal mucosa. Dysfunction of the mucus layer and bacterial infiltration are linked to tissue inflammation and disease. To study host-bacterial interactions at the mucosal interface, we created an experimental model that contains luminal space, a mucus layer, an epithelial layer, and suspended immune cells. Reconstituted porcine small intestinal mucus formed an 880 ± 230 µm thick gel layer and had a porous structure. In the presence of mucus, sevenfold less probiotic and nonmotile VSL#3 bacteria transmigrated across the epithelial barrier compared to no mucus. The higher bacterial transmigration caused immune cell differentiation and increased the concentration of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α; p < .01). Surprisingly, the mucus layer increased transmigration of pathogenic Salmonella and increased secretion of TNF-α and IL-8 (p < .05). Nonmotile, flagella knockout Salmonella had lower transmigration and caused lower IL-8 and TNF-α secretion (p < .05). These results demonstrate that motility enables pathogenic bacteria to cross the mucus and epithelial layers, which could lead to infection. Using an in vitro coculture platform to understand the interactions of bacteria with the intestinal mucosa has the potential to improve the treatment of intestinal diseases.
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Project description:Previous studies suggested that activation of the innate immune system impairs the induction of transplantation tolerance, but the responsible inflammatory mediators have not been identified. In this study, we examined whether IL-6 and TNF-alpha promote resistance to transplantation tolerance. Using a highly immunogenic murine skin allograft model, we found that the absence of both IL-6 and TNF-alpha in the graft recipient synergized with co-stimulatory blockade to induce tolerance. Furthermore, IL-6 and TNF-alpha acted together to promote T cell alloimmune responses both in vitro and in vivo and to impair the ability of regulatory T cells to suppress effector T cell alloimmunity. In addition, deficiency of recipient IRAK-M, a negative regulator of certain innate immune pathways, augmented cellular IL-6 and TNF-alpha responses and impaired the ability of co-stimulatory blockade to extend allograft survival. In summary, IL-6 and TNF-alpha synergistically impair the efficacy of therapies that promote allograft acceptance.
| S-EPMC2678042 | biostudies-literature
Project description:Rel A (p65) ChIP-chip using polyclonal antibody (N-terminus) performed on TNF-alpha-stimulated HeLaS3 cells for Nimblegen ENCODE arrays which comprise 50mer oligonucleotides spaces every 38bps (overlapping by 12nts). Goal was to identify p65-binding regions in the inflammatory and immune response of human cells. Keywords: ChIP-chip
2007-02-14 | GSE6900 | GEO
Project description:Premature adrenarche (PA), the early rise in adrenal androgen production leading to prepubertal signs of androgen action, has been connected with adverse metabolic features. The metabolic syndrome is characterized by low-grade inflammation which in turn is associated with increases in circulating proinflammatory cytokines, like tumor necrosis factor-alpha (TNF-?) and interleukin-6 (IL-6). We tested the hypothesis that serum concentrations of TNF-? and IL-6 are increased in PA by studying 73 children with PA and 98 age- and gender-matched controls. Serum TNF-? and IL-6 concentrations were measured using a multiplex bead array. The subjects were genotyped for the TNF-? gene -308 G?>?A polymorphism (known to affect TNF-? gene transcription), and genotype-phenotype associations were studied. The mean serum TNF-? concentration was higher in the PA than control children (20.4 vs. 18.4?pg/ml, P?=?0.048), whereas there was no significant difference in the mean serum IL-6 concentrations between the study groups. The difference in TNF-? was not explained by excess body weight in the PA subjects as the difference remained significant after BMI-adjustment (P?=?0.038). In the PA group, TNF-? concentration was not associated with metabolic-endocrine features, but high IL-6 was associated with lower birth weight. There was no difference in the genotype distribution of the TNF-? gene -308 G?>?A polymorphism between the PA and control groups. In conclusion, PA was associated with increased serum TNF-? concentrations which, unexpectedly, were not connected with BMI or insulin resistance. The TNF-? gene -308 G?>?A polymorphism does not seem to be associated with the development of PA.
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