Protection of mouse by blockade to TNF-α signaling is due to inhibition against IL-17A
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE199821 | GEO | 2023/11/08
REPOSITORIES: GEO
Similar Datasets
Project description:Tumor necrosis factor alpha induces vascular permeability, playing an important role in inflammation. Also, TNF-induced vascular leakage is involved in the increased extravasation of nanoparticle formulated chemotherapeutics improving drug delivery and subsequently tumor response, and we found a positive correlation between the presence of pericytes in the tumor-associated vasculature and TNF-induced leakage. RNA sequencing and pathway analysis of TNF-stimulated versus non-stimulated pericytes and endothelial cells show significant upregulation of several pathways involving interferon regulating pathways with a high expression of CXCL10, also known as Interferon gamma-inducible protein 10 (IP-10) in TNF-stimulated pericytes. In addition, CXCL10 protein production was significantly increased in conditioned medium from TNF-exposed pericytes compared to the other conditions. In our animal studies, we observed that tumor types with high pericyte covered vessels show enhanced permeability when exposed to TNF, which can be blocked with a neutralizing CXCL10 antibody. Vice versa, tumors with vessels low in pericyte number do not respond to TNF, i.e., do not express elevated permeability. Importantly, this lack of pericyte coverage can be compensated by co-administration of CXCL10. Our finding reveals a mechanism where TNF induces CXCL10 release from pericytes, being at the basis of increased permeability and thus vascular leakage.
2022-07-01 | GSE203505 | GEO
Project description:Analysis of MIN6 murine beta cell line transfected with Pla2g6 RNAi and treated with pro-inflammatory cytokines TNF-alpha, IL-1beta and IFN-gamma.
2024-02-08 | PXD017863 | Pride
Project description:Transcriptional activation of cultured mouse astrocytes in response to stimulation with CCM (complete cytokine mix: TNF-alpha, IL1-beta and IFN-gamma) at 4hr and 16hr time points.
2005-12-01 | E-MEXP-321 | biostudies-arrayexpress
Project description:G-protein coupled receptors (GPCRs) have diverse roles in physiological processes, including immunity. Gs-coupled GPCRs increase while Gi-coupled ones decrease intracellular cAMP. Previous studies suggest that, in epithelial cells, Gs-coupled GPCRs enhance whereas Gi-coupled GPCRs suppress pro-inflammatory immune responses. In order to examine the issue, we chose beta2 adrenergic receptor and GPR40 as representatives of Gs- and Gi- coupled GPCRs, respectively, and examined their effects on TNF-alpha and IFN-gamma-(TNF-alpha + IFN-gamma) induced gene expression by HaCaT. We used microarrays to detail the global changes of gene expression induced by a beta2 adrenergic receptor agonist terbutaline or GPR40 agonist GW9508 pre-treatment in TNF-alpha + IFN-gamma - stimulated HaCaT cells. HaCaT cells were pre-treated with terbutaline or GW9508, TNF-alpha + IFN-gamma were then added, and cultured for another 24 h. Cells were then used for RNA extraction and hybridization on Affymetrix microarrays. We sought to clarify changes in gene expression after 1) TNF-alpha + IFN-gamma, 2) TNF-alpha + IFN-gamma + terbutaline, and 3) TNF-alpha + IFN-gamma + GW9508 treatment. To this end, we set 4 groups of samples; 1) unstimulated group, 2) TNF-alpha + IFN-gamma-stimulated group, 3) TNF-alpha + IFN-gamma + terbutaline-stimulated group, and 4) TNF-alpha + IFN-gamma + GW9508-stimulated group. In each group, HaCaT cells were stimulated in triplicate wells (n=3).
2010-12-01 | E-GEOD-20297 | biostudies-arrayexpress
Project description:Systemic lupus erythematosus (SLE) is characterized by increased vascular risk due to premature atherosclerosis independent of traditional risk factors. We previously proposed that interferon-α plays a crucial role in premature vascular damage in SLE. IFN-α alters the balance between endothelial cell apoptosis and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic cells (CACs). Here we demonstrate that IFN-α promotes an antiangiogenic signature in SLE and control EPCs/CACs, characterized by transcriptional repression of IL-1α and β, IL-1 receptor 1 and vascular endothelial growth factor A (VEGF-A) and upregulation of IL-1 receptor antagonist (IL-1RN) and the decoy receptor IL1-R2. IL-1β promotes significant improvement in the functional capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN-α. We used microarrays to analyze the effect of IFNα on peripheral blood EPCs/CACs and on bone marrow EPCs exposed to proangiogenic stimulation. Human healthy EPCs from bone marrow were isolated and cultured under proangiogenic stimulation; after IFNa incubation or not, RNA was extracted and processed for hybridization on Affymetrix microarrays.
2011-04-13 | E-GEOD-26951 | biostudies-arrayexpress
Project description:Systemic lupus erythematosus (SLE) is characterized by increased vascular risk due to premature atherosclerosis independent of traditional risk factors. We previously proposed that interferon-α plays a crucial role in premature vascular damage in SLE. IFN-α alters the balance between endothelial cell apoptosis and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic cells (CACs). Here we demonstrate that IFN-α promotes an antiangiogenic signature in SLE and control EPCs/CACs, characterized by transcriptional repression of IL-1α and β, IL-1 receptor 1 and vascular endothelial growth factor A (VEGF-A) and upregulation of IL-1 receptor antagonist (IL-1RN) and the decoy receptor IL1-R2. IL-1β promotes significant improvement in the functional capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN-α. We used microarrays to analyze the effect of IFNα on peripheral blood EPCs/CACs and on bone marrow EPCs exposed to proangiogenic stimulation. This SuperSeries is composed of the SubSeries listed below. Human healthy and lupus EPCs and CACs from PBMCs, and healthy EPCs from bone marrow, were isolated and cultured under proangiogenic stimulation; after IFN-α incubation or not, RNA was extracted and processed for hybridization on Affymetrix microarrays.
2011-04-13 | E-GEOD-23203 | biostudies-arrayexpress
Project description:Systemic lupus erythematosus (SLE) is characterized by increased vascular risk due to premature atherosclerosis independent of traditional risk factors. We previously proposed that interferon-α plays a crucial role in premature vascular damage in SLE. IFN-α alters the balance between endothelial cell apoptosis and vascular repair mediated by endothelial progenitor cells (EPCs) and myeloid circulating angiogenic cells (CACs). Here we demonstrate that IFN-α promotes an antiangiogenic signature in SLE and control EPCs/CACs, characterized by transcriptional repression of IL-1α and β, IL-1 receptor 1 and vascular endothelial growth factor A (VEGF-A) and upregulation of IL-1 receptor antagonist (IL-1RN) and the decoy receptor IL1-R2. IL-1β promotes significant improvement in the functional capacity of lupus EPCs/CACs, therefore abrogating the deleterious effects of IFN-α. We used microarrays to analyze the effect of IFNα on peripheral blood EPCs/CACs and on bone marrow EPCs exposed to proangiogenic stimulation. Human lupus EPCs and CACs from PBMCs were isolated and cultured under proangiogenic stimulation; after IFNa incubation or not, RNA was extracted and processed for hybridization on Affymetrix microarrays.
2011-04-13 | E-GEOD-26950 | biostudies-arrayexpress
Project description:Inflammation is beneficial when it is part of the innate immune response, but harmful when it occurs in an unregulated, chronic manner. We now report that IkappaB-beta, a member of the classical IkappaB family, serves a dual role of both inhibiting and facilitating the inflammatory response. IkappaB-beta degradation releases NF-kappaB dimers which upregulate proinflammatory target genes such as TNF-alpha. Suprisingly absence of IkappaB-beta results in a dramatic reduction of TNF-alpha in response to LPS even though the activation of NF-kappaB is normal. The inhibition of TNF-alpha mRNA expression can be correlated to the absence of nuclear, hypophosphorylated-IkappaB-beta bound to p65:cRel heterodimers at a specific kappaB site on the TNF-alpha promoter. Therefore IkappaB-beta acts through p65:cRel dimers to maintain prolonged expression of TNF-alpha. As a result, IkappaB-beta knockout mice are resistant to LPS induced septic shock and collagen-induced arthritis, and therefore blocking IkappaB-beta might be a promising new strategy for selectively inhibiting the chronic phase of TNF-alpha producting during the inflammatory response. Wild type and IkappaB-beta knockout BMDM cells were stimulated with LPS(1ug/ml) for 0, 1, and 5 hours. RNA isolated from the cells was analyzed on Affymetrix Mouse Genome 430A 2.0 gene expression chip.
2010-06-16 | E-GEOD-22223 | biostudies-arrayexpress
Project description:SLE patients are always with various disease manifestation. Various cytokines are pointed interacting and playing pathological roles in SLE although the etiopathology is still obscure. In this study, we aimed to investigate the effects of cytokine interactions in the immune response of SLE patients. Overexpressed interferon-inducible(IFI) genes were confirmed in peripheral blood from SLE patients. Using network-based analysis on the immune response-related genes, several networks including cytokines such as TNF and IFN-γ, or beta-estradiol(E2), were constructed. TNF-regulated genes were dominant in these networks but in vitro TNF stimulation on PBMCs showed no different responses in the expressions of these genes between SLE and healthy individuals. Co-stimulating experiments by TNF, IFN-γ, and E2 with IFN-α, revealed that TNF has repressive while IFN-γ essentially has synergistic effect with IFN-α on IFI gene expressions in vitro. E2 showed different effects on IFI gene expressions among 3 individuals.
2009-06-01 | GSE12374 | GEO
Project description:SLE patients are always with various disease manifestation. Various cytokines are pointed interacting and playing pathological roles in SLE although the etiopathology is still obscure. In this study, we aimed to investigate the effects of cytokine interactions in the immune response of SLE patients. Overexpressed interferon-inducible(IFI) genes were confirmed in peripheral blood from SLE patients. Using network-based analysis on the immune response-related genes, several networks including cytokines such as TNF and IFN-γ, or beta-estradiol(E2), were constructed. TNF-regulated genes were dominant in these networks but in vitro TNF stimulation on PBMCs showed no different responses in the expressions of these genes between SLE and healthy individuals. Co-stimulating experiments by TNF, IFN-γ, and E2 with IFN-α, revealed that TNF has repressive while IFN-γ essentially has synergistic effect with IFN-α on IFI gene expressions in vitro. E2 showed different effects on IFI gene expressions among 3 individuals. Peripheral blood was obtained from patients with SLE (n=11) and healthy women (n=6). Gene expression profile was analyzed using DNA microarray covering 30,000 human genes. Differentially expressed immune response-related genes were selected and analyzed by using Expression Analysis Systemic Explorer (EASE) based on Gene Ontology (GO) followed by network pathway analysis with Ingenuity Pathways Analysis (IPA).
2009-05-31 | E-GEOD-12374 | biostudies-arrayexpress