Gene expression profile at single cell level of DC from B16F10 tumor with Advs treatment
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE223344 | GEO | 2023/02/13
REPOSITORIES: GEO
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Project description:Expression of CD40 in non-hematopoietic cells has been linked to inflammation. We presented evidence that CD40, a T-cell costimulatory molecule, is expressed in human β-cells and the engagement of CD40 in insulinoma cells activated the NFKB and ERK1/2 pathways. CD40 activation in human islets cells induced secretion of IL-8, MCP-1 and MIP-1 β, which is abrogated by inhibitors of NFkB and ERK1/2 inhibitors. In this study, we have studied gene expression mediated by CD40-CD40L interaction in islet cells. This approach identified 90 genes and transcripts exhibiting at least a 1.7 fold increase in their expression intensity after treatment with soluble CD40L. A significant number of genes were related to inflammation and oxidative stress. We have a strong overexpression of CXCL1 (Groα), CXCL2 (Mif2) and CXCL3; chemokines belonging to CXC family structurally related to Il-8. 11 genes were selected from this group and further quantified by Real Time PCR, including CXCL1. Activation of islet cells with CD40L induced the secretion of CXCL1 in a NFKB dependent manner. Engagement of CD40 in islet cells did not induce apoptosis, neither β-cell death and did not enhanced TNF-α mediated cell death as observed in insulinoma cells. CD40 activation in insulinoma cells, results in ERK1/2 dependent phsophorylation of synapsin I, a protein associated with the exocytosis machinery in neurons and β-cells. However, treatment of islets with soluble CD40L did not affect glucose induced insulin secretion. It has been reported that ductal cells always present in human islet preparations express CD40 constitutively (ref). We found that CD40-CD40L interaction in ductal cells, unlike in β-cells, induces secretion of diabetogenic cytokines IFNγ and TNF-α. Furthermore, incubation of islets containing ductal cells with CD40L decreased β-cells viability as assessed by measurement of their mitochondrial membrane potential Experiment Overall Design: We isolated islet cells from three patients. Part of islet cells from each patient has been treated with CD40L. We compared gene expression in treated cells vs untreated for each patient using dye-swap.
2008-10-20 | E-GEOD-8873 | biostudies-arrayexpress
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2009-02-21 | E-GEOD-10601 | biostudies-arrayexpress
Project description:The CD40-CD40L dyad seems to play a prominent role fostering the immune-inflammatory response triggered by endothelial cell (EC)-T cell interaction. To comprehensively delineate the involvement of CD40 (TNFRSF5) in EC activation, we combined RNAi-mediated CD40 knock-down with comparative genome-wide transcriptional profiling of EC in response to T cell. We report the initiation of a profound stress response in ECs upon CD40-CD40L engagement through early up-regulation, among others, of the major pro-inflammatory NFkB and MAPK/SAPK pathways and their associated transcription factors. Moreover, we have identified novel genes regulated through the CD40-CD40L interaction, and pathways previously unrecognized to be induced by CD40 signaling in ECs. Thus, we document a strong down-regulation of endothelial APLN by CD40-CD40L interaction, which could lead to vascular tone dysfunction in atherosclerotic lesions. Conversely, CD40-mediated up-regulation of the viral immune surveillance system, notably TLR3, IFIH1, RIG-I, and RNASEL, establishes a reverse link from adaptive to innate immunity in ECs. Moreover, systematic enrichment analysis substantiates endothelial CD40 involvement in the transcriptional regulation of gene networks associated with adhesion and motility, immunity, cell fate control, hemostasis and metabolism. Our study also highlights the potency and specificity of CD40 siRNA mediated inhibition, and the relevance of CD40 signaling pathways for anti-inflammatory therapeutic intervention. Keywords: treated vs. untreated comparison, time course
2009-02-10 | GSE10601 | GEO
Project description:Expression of CD40 in non-hematopoietic cells has been linked to inflammation. We presented evidence that CD40, a T-cell costimulatory molecule, is expressed in human β-cells and the engagement of CD40 in insulinoma cells activated the NFKB and ERK1/2 pathways. CD40 activation in human islets cells induced secretion of IL-8, MCP-1 and MIP-1 β, which is abrogated by inhibitors of NFkB and ERK1/2 inhibitors. In this study, we have studied gene expression mediated by CD40-CD40L interaction in islet cells. This approach identified 90 genes and transcripts exhibiting at least a 1.7 fold increase in their expression intensity after treatment with soluble CD40L. A significant number of genes were related to inflammation and oxidative stress. We have a strong overexpression of CXCL1 (Groα), CXCL2 (Mif2) and CXCL3; chemokines belonging to CXC family structurally related to Il-8. 11 genes were selected from this group and further quantified by Real Time PCR, including CXCL1. Activation of islet cells with CD40L induced the secretion of CXCL1 in a NFKB dependent manner. Engagement of CD40 in islet cells did not induce apoptosis, neither β-cell death and did not enhanced TNF-α mediated cell death as observed in insulinoma cells. CD40 activation in insulinoma cells, results in ERK1/2 dependent phsophorylation of synapsin I, a protein associated with the exocytosis machinery in neurons and β-cells. However, treatment of islets with soluble CD40L did not affect glucose induced insulin secretion. It has been reported that ductal cells always present in human islet preparations express CD40 constitutively (ref). We found that CD40-CD40L interaction in ductal cells, unlike in β-cells, induces secretion of diabetogenic cytokines IFNγ and TNF-α. Furthermore, incubation of islets containing ductal cells with CD40L decreased β-cells viability as assessed by measurement of their mitochondrial membrane potential Keywords: Pancreas, Islets of Langerhans, chemokines, cytokines, inflammation, apoptosis, Nuclear Factor-κB(NFκB)
2008-08-01 | GSE8873 | GEO
Project description:Gene expression profile at single cell level of DC from B16F10 tumor with Advs treatment
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Project description:The interaction between the transmembrane glycoprotein surface receptor CD40 expressed by skin keratinocytes (KCs) and its T cell-expressed ligand CD154 was suggested to exacerbate inflammatory skin diseases. However, the full spectrum of CD40-mediated effects by KCs underlying this observation is unknown. Therefore, changes in gene expression after CD40 ligation of KCs were studied by microarrays. CD40-mediated activation for 2 hours stimulated the expression of a coordinated network of immune-involved genes strongly interconnected by IL8 and TNF, while after 24 hours anti-proliferative and anti-apoptotic genes were upregulated. CD40 ligation stimulated the production of chemokines that attracted lymphocytes and myeloid cells from peripheral blood mononuclear cells (PBMCs). Thus, CD40-mediated activation of KCs resulted in a highly coordinated response of genes required for the local development and sustainment of adaptive immune responses. The importance of this process was confirmed by a study on the effects of human papilloma virus (HPV) infection to the KCâs response to CD40 ligation. HPV infection clearly attenuated the magnitude of the response to CD40 ligation and consequently the KCâs capacity to attract PBMCs. The fact that HPV attenuates CD40 signalling in KCs indicates the importance of the CD40-CD154 immune pathway in boosting cellular immunity within epithelia. Total RNA from eight 72 hours 50 IU/ml IFNgamma pre-stimulated primary undifferentiated keratinocyte cultures, four uninfected and four HPV-positive, that were either left unstimulated, or stimulated for 2 hours with IFNgamma and Control- or CD40L-expressing L-cells (mouse fibroblasts), or stimulated for 24 hours with IFNgamma and Control- or CD40L-expressing L-cells. The stimulated samples were generated in duplo. 72 samples were generated in total.
2015-10-26 | E-GEOD-54181 | biostudies-arrayexpress