Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA261256 | ENA |
REPOSITORIES: ENA
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Project description:Hyporesponsiveness by phagocytes, a well-known phenomenon in sepsis, is frequently induced by low-dose endotoxin-stimulation of Toll-like-receptor-4 (TLR4) but can also be found under sterile inflammatory conditions. We now demonstrate that the endogenous alarmins myeloid-related protein (MRP) 8 and MRP14 induce phagocyte hyporesponsiveness via chromatin modifications in a TLR4-dependent manner resulting in enhanced survival during murine septic shock. Also during sterile inflammation, polytrauma and burn patients present with initially high MRP serum concentrations identifying these proteins as obvious candidates for triggering secondary hyporesponsiveness in these patients. Interestingly, increased peripartal MRP concentrations prime human neonatal phagocytes for hyporesponsiveness, which was confirmed in murine neonatal endotoxinemia in wildtype and MRP14 -/- mice. Using a comparative bioinformatics analysis between genome-wide response patterns of MRP- and LPS- tolerized monocytes we demonstrated no difference in global gene expression between samples pretreated with either MRP8-MRP14 or LPS. Our data indicate that alarmin-triggered phagocyte tolerance represents a novel regulatory mechanism for the susceptibility of neonates to systemic infections and during sterile inflammation. Human blood monocytes prestimulated with MRP8-MRP14 or LPS and afterwards activated with LPS were selected for RNA extraction and hybridization on Illumina microarrays.
2014-12-12 | E-GEOD-61477 | biostudies-arrayexpress
Project description:Hyporesponsiveness by phagocytes, a well-known phenomenon in sepsis, is frequently induced by low-dose endotoxin-stimulation of Toll-like-receptor-4 (TLR4) but can also be found under sterile inflammatory conditions. We now demonstrate that the endogenous alarmins myeloid-related protein (MRP) 8 and MRP14 induce phagocyte hyporesponsiveness via chromatin modifications in a TLR4-dependent manner resulting in enhanced survival during murine septic shock. Also during sterile inflammation, polytrauma and burn patients present with initially high MRP serum concentrations identifying these proteins as obvious candidates for triggering secondary hyporesponsiveness in these patients. Interestingly, increased peripartal MRP concentrations prime human neonatal phagocytes for hyporesponsiveness, which was confirmed in murine neonatal endotoxinemia in wildtype and MRP14 -/- mice. Using a comparative bioinformatics analysis between genome-wide response patterns of MRP- and LPS- tolerized monocytes we demonstrated no difference in global gene expression between samples pretreated with either MRP8-MRP14 or LPS. Our data indicate that alarmin-triggered phagocyte tolerance represents a novel regulatory mechanism for the susceptibility of neonates to systemic infections and during sterile inflammation.
2014-12-12 | GSE61477 | GEO
Project description:The prohormone convertase 1/3 (PC1/3) is an enzyme playing an important role in the processing of precursor proteins involved in neuroimmune phenotype of neuroendocrine cells. The expression of PC1/3 is not only restricted to neuroendocrine tissues; recent studies reported a role of PC1/3 in Toll-like receptor immune response in macrophages. Here, using lentivirus strategy, we investigated the consequences of PC1/3 down-regulation with the aim of understanding the intracellular impact of such inhibition and its biological application to cancer therapy. Under sterile conditions, we demonstrated that PC1/3 inactivated macrophages express a M1-like phenotype characterized by filopodia extensions, pro-inflammatory chemokines and cytokines secretion (IL6, CXCL10; TNF) and TLR4 Myd88 dependent signaling activation. Under LPS challenge, PC1/3 KO cells secrete through store-operated calcium entry increase, a cocktail of pro-inflammatory factors including alarmins and chemokines conducting to attract naïve T helper lymphocytes (Th0) which favors cytotoxic response. Tests perform with the secreted factors by the challenged PC1/3 KO cells on breast and ovarian cancer cells (SKBR3, SKOV3) establish that the factors secreted are able to inhibit both viability and resistance to chemotherapies. Under inhibitory conditions using IL-10, the PC1/3 KO cells still continue to produce inflammatory cytokines and anti-tumoral factors. Taken together, these data establish that inhibition of PC1/3 can be used as a potential immune therapy for awaking intra-tumoral macrophages.
2015-09-09 | PXD001984 | Pride
Project description:The prohormone convertase 1/3 (PC1/3) is an enzyme playing an important role in the processing of precursor proteins involved in neuroimmune phenotype of neuroendocrine cells. The expression of PC1/3 is not only restricted to neuroendocrine tissues; recent studies reported a role of PC1/3 in Toll-like receptor immune response in macrophages. Here, using lentivirus strategy, we investigated the consequences of PC1/3 down-regulation with the aim of understanding the intracellular impact of such inhibition and its biological application to cancer therapy. Under sterile conditions, we demonstrated that PC1/3 inactivated macrophages express a M1-like phenotype characterized by filopodia extensions, pro-inflammatory chemokines and cytokines secretion (IL6, CXCL10; TNF) and TLR4 Myd88 dependent signaling activation. Under LPS challenge, PC1/3 KO cells secrete through store-operated calcium entry increase, a cocktail of pro-inflammatory factors including alarmins and chemokines conducting to attract naïve T helper lymphocytes (Th0) which favors cytotoxic response. Tests perform with the secreted factors by the challenged PC1/3 KO cells on breast and ovarian cancer cells (SKBR3, SKOV3) establish that the factors secreted are able to inhibit both viability and resistance to chemotherapies. Under inhibitory conditions using IL-10, the PC1/3 KO cells still continue to produce inflammatory cytokines and anti-tumoral factors. Taken together, these data establish that inhibition of PC1/3 can be used as a potential immune therapy for awaking intra-tumoral macrophages.
2015-09-15 | PXD001986 | Pride
Project description:The alarmins myeloid-related protein (MRP) 8 and MRP14 are the dominant cytoplasmic proteins in phagocytes. After release by activated phagocytes extracellular MRP8/MRP14 complexes promote inflammation in many diseases, including infections, allergies, autoimmune diseases, rheumatoid arthritis or inflammatory bowel disease. As receptors for the pro-inflammatory effects of human MRP8, the active component of the MRP8/MRP14-complex, Toll-like receptor (TLR) 4 and the multi-ligand receptor of advanced glycation end products (RAGE) are controversial discussed. Using a comparative bioinformatics analysis between genome-wide response patterns of monocytes to MRP8, endotoxin and different cytokines we demonstrated a dominant role of TLR4 during MRP8-mediated phagocyte activation. The relevance of this signaling pathway could be confirmed in independent cell models for TLR4 and RAGE dependent signaling in mouse and man. In addition to well-known proinflammatory functions of MRP8 our systems biology approach unraveled a novel anti-apoptotic effect of MRP8 on monocytes which was confirmed in independent functional experiments. Our data define the dominance of the TLR4-MRP8 axis in activation of human phagocytes which represents a novel attractive target for modulation of overwhelming innate immune responses. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process. Human blood monocyte stimulated with various stimuli (control, MRP8, LPS, TNF, IL1) were selected for RNA extraction and hybridization on Affymetrix microarrays.
2014-12-12 | E-GEOD-56681 | biostudies-arrayexpress
Project description:We showed different function of monocyte derived cells in the lamina propria of the colon under steady state and inflammatory conditions. We used microarrays to detail the global programme of gene expression and identified distinct clusters of regulated genes during this process. Different subsets of mononuclear phagocytes were sorted from the colonic lamina propria as well as the spleen. Sorting was done in C57BL/6 mice in steady state and under inflammatory conditions (Dextran Sodium Sulphate induced colitis model)
2012-11-08 | E-GEOD-42101 | biostudies-arrayexpress
Project description:Expression Array of Lymphoblastoid Cell lines Under Inflammatory Conditions
| PRJNA134021 | ENA
Project description:Monocytic cell differentiation from band-stage neutrophils under inflammatory conditions
| PRJNA253926 | ENA
Project description:The alarmins myeloid-related protein (MRP) 8 and MRP14 are the dominant cytoplasmic proteins in phagocytes. After release by activated phagocytes extracellular MRP8/MRP14 complexes promote inflammation in many diseases, including infections, allergies, autoimmune diseases, rheumatoid arthritis or inflammatory bowel disease. As receptors for the pro-inflammatory effects of human MRP8, the active component of the MRP8/MRP14-complex, Toll-like receptor (TLR) 4 and the multi-ligand receptor of advanced glycation end products (RAGE) are controversial discussed. Using a comparative bioinformatics analysis between genome-wide response patterns of monocytes to MRP8, endotoxin and different cytokines we demonstrated a dominant role of TLR4 during MRP8-mediated phagocyte activation. The relevance of this signaling pathway could be confirmed in independent cell models for TLR4 and RAGE dependent signaling in mouse and man. In addition to well-known proinflammatory functions of MRP8 our systems biology approach unraveled a novel anti-apoptotic effect of MRP8 on monocytes which was confirmed in independent functional experiments. Our data define the dominance of the TLR4-MRP8 axis in activation of human phagocytes which represents a novel attractive target for modulation of overwhelming innate immune responses. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.
2014-12-12 | GSE56681 | GEO
Project description:To identify novel microRNAs that are associated with drought tolerance in two different cowpea genotypes, we generated small RNA sequences from adult cowpea plants under control and dought stress treatments. Over 79 million raw reads were generated and numerous novel microRNAs are identified, including some associated with drought tolerance. Sequencing of small RNAs in two cowpea genotypes under control and drought stress conditions.
2011-09-01 | E-GEOD-26402 | biostudies-arrayexpress