Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA315121 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The Mrp8 and Mrp14 proteins (calprotectin) accumulate within tissues during aging and may contribute to chronic inflammation. To address this possibility, we evaluated calprotectin-deficient Mrp14-KO and wild-type (WT) mice at 5 and 24 months of age. However, there was no evidence that age-related inflammation is blunted in KO mice. Inflammation makers were in fact elevated in livers from old KO mice, and microarray analysis revealed more consistent elevation of genes specifically expressed by B-cells and T-cells. Adipose-specific genes, however, were less consistently elevated in aged KO mice, suggesting an anti-steatosis effect of Mrp8/14 deficiency. Consistent with this, genes decreased by the anti-steatosis agent SRT1720 were decreased in old KO compared to old WT mice. Expression of lipid metabolism genes was altered in KO mice at 5 months of age, along with genes associated with development, biosynthesis and immunity. These early-age effects of Mrp8/14 deficiency, in the absence of any external stressor, were unexpected. Taken together, our findings demonstrate a pro-steatosis rather than pro-inflammatory role of calprotectin within the aging liver. This appears to reflect a developmental-metabolic phenotype of Mrp14-KO mice that is manifest at a young age in the absence of pro-inflammatory stimuli.
2017-02-09 | GSE79182 | GEO
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: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:CPEB4 prevents hepatic steatosis
| PRJNA322835 | ENA
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:Examining the effect of CMPF treatment in the livers of mice. This study examines both the prevention and reversal of steatosis. We used arrays to determine the pathways through which CMPF prevents and reverses steatosis
2017-11-08 | GSE106639 | GEO
Project description:Interventions: IHC of MMR proteins, genetic or epigenetic analyses of MMR genes
Primary outcome(s): Screening of HNPCC related tumors by IHC for loss of MMR protein expression and observation of the clinical features assciated with MMR deficiency.
Study Design: Single arm Non-randomized
| 2621222 | ecrin-mdr-crc
Project description:Recent findings suggest that the human APOE epsilon 4 allele protects against non-alcoholic fatty liver disease, while APOE epsilon 3 promotes hepatic steatosis and steatohepatitis. We performed an untargeted proteome analysis of the liver and identified a great number of proteins differently expressed in obese APOE3 and APOE4 mice. The majority of the proteins up-regulated in APOE3 can be grouped to inflammation and damage-associated response, cytoskeleton and lipid storage. In contrast, those proteins that are up-regulated in APOE4 can be related to intermediate filament modifications, biotransformation and amino acid metabolism. Results of the targeted quantitative RT-PCR and Western blot experiments contribute to the overall finding that APOE3 promotes hepatic steatosis, inflammatory- and damage-associated response signaling and fibrosis in the liver of obese mice. One of the proteins that were up-regulated in obese as well as lean APOE4 compared to APOE3 mice is parvulin 14 (Pin4). Up-regulation of parvulin 14 may be involved in the protection against fatty liver disease evident in the presence of APOE4.
2024-05-21 | PXD033973 | Pride