Severe infections and sepsis is an increasing clinical problem that cause prolonged morbidity and substantial mortality. At present, antibiotics are essentially the only pharmacological treatment for sepsis. The incidence of antibiotic resistance is increasing and it is therefore critical to find new therapies for sepsis. Staphylococcus aureus (S. aureus) is a major cause of septic mortality. Neutrophils play a major role in defense against bacterial infections. We have recently shown that a saturated high fat diet decreases survival in septic mice, but the mechanisms behind remain elusive. The aim of the present study was to investigate how the dietary fat composition affects survival and neutrophils function after experimental septic infection in mice. We found that, after S. aureus infection, mice fed polyunsaturated high fat diet (HFD/P) for 8 weeks had increased septic survival and decreased bacterial load compared with mice fed saturated HFD (HFD/S), and similar to that of mice given low fat diet (LFD). Furthermore, uninfected mice fed HFD/P had increased number of Ly6G+ neutrophils in bone marrow. In addition, mice fed HFD/P had a higher number Ly6G+ neutrophils recruited to the site of inflammation after peritoneal injection of thioglycollate. In conclusion, polyunsaturated dietary fat increased both survival and the efficiency of the bacterial clearance during septic S. aureus infection. Moreover, this diet enhanced the number and chemotaxis of neutrophils, a key component of the immune response to S. aureus infections.
Dietary polyunsaturated fatty acids increase survival and decrease bacterial load during septic Staphylococcus aureus infection and improve neutrophil function in mice.
Sex, Specimen part
View SamplesThe protease activity of the paracaspase MALT1 plays an important role in antigen receptor-mediated lymphocyte activation by controlling the activity of the transcription factor NF-kB and is thus essential for the expression of inflammatory target genes.
MALT1 Protease Activity Controls the Expression of Inflammatory Genes in Keratinocytes upon Zymosan Stimulation.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Sex, Age, Specimen part, Time
View SamplesAnalysis of effect of long-term cryopreservation on peripheral blood mononuclear cells at gene expression level. The hypothesis tested in the present study was that long-term cryopreservation has an influence on the transcriptome profile of peripheral blood mononuclear cells. Results indicated remarkable changes in expression patterns upon cryopreservation of PBMCs, with decreasing signal intensities over time.
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Sex, Age, Specimen part, Time
View SamplesAnalysis of cryopreservation effects on peripheral blood mononuclear cells at gene expression level. The hypothesis tested in the present study was that cryopreservation has an influence on the transcriptome profile of peripheral blood mononuclear cells. Results indicated remarkable changes in expression patterns upon cryopreservation of PBMCs, with a strong loss of signal intensities to background levels for several transcripts.
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Age, Specimen part
View SamplesAnalysis of long-term freezing on the stability of transcriptome profiles in PAXgene stabilized whole blood samples. In the present study it was tested if long-term freezing of PAXgene RNA tubes (up to one year) has an influence on the transcriptome profile of peripheral whole blood samples. Results indicated that gene expression profiles of whole blood samples stabilized with PAXgene RNA tubes remain stable for at least 1 year.
RNA-stabilized whole blood samples but not peripheral blood mononuclear cells can be stored for prolonged time periods prior to transcriptome analysis.
Sex, Age, Specimen part, Time
View SamplesDiffuse large B-cell lymphoma (DLBCL) represents the most common form of lymphoma. We could show that in DLBCL cell lines the transcription factor NFAT is constitutively activated and drives the survival of a DLBCL subset. Aim of the analysis was to identify NFAT target genes in a NFAT-dependent (HBL-1) or -independent (HT) DLBCL cell line. To block NFAT activity, the DLBCL cells were treated with the calcineurin inhibitor cyclosporin A (CsA) up to 48 h. With this approach, we identified several survival-related NFAT target genes in HBL-1 cells that might explain the toxic effects of calcineurin inhibitors.
Targeting chronic NFAT activation with calcineurin inhibitors in diffuse large B-cell lymphoma.
Treatment
View SamplesWe used microarrays to detail the global gene expression changes following apical infection of porcine choroid plexus epithelial cells (PCPEC) with Streptococcus suis (S. suis)
In vitro transcriptome analysis of porcine choroid plexus epithelial cells in response to Streptococcus suis: release of pro-inflammatory cytokines and chemokines.
Specimen part
View SamplesWNT-induced secreted protein 1 (WISP1/CCN4), a member of the CCN protein family, acts as a downstream factor of the canonical WNT-signaling pathway. A dysregulated expression of WISP1 often reflects its oncogenic potential by inhibition of apoptosis, a necessary form of cell death that protect cell populations for transformation into malignant phenotypes. WISP1-signaling is also known to affect proliferation and differentiation of human mesenchymal stem cells (hMSCs), which are fundamental for the constitution and maintenance of the musculoskeletal system. Our study emphasizes the importance of WISP1-signaling for cell survival of primary human cells. Therefore, we established a successful down-regulation of endogenous WISP1 transcripts through gene silencing in hMSCs. We were able to demonstrate the consequence of cell death immediately after WISP1 down-regulation took place. Bioinformatical analyses of subsequent performed microarrays from WISP1 down-regulated vs. control samples confirmed this observation. We uncovered several clusters of differential expressed genes important for cellular apoptosis induction and immuno-regulatory processes, thereby indicating TRAIL-induced and p53-mediated apoptosis as well as IFNbeta-signaling. Since all of them act as potent inhibitors for malignant cell growth, in vitro knowledge about the connection with WISP1-signaling could help to find new therapeutic approaches concerning cancerogenesis and tumor growth in musculoskeletal tissues.
WISP 1 is an important survival factor in human mesenchymal stromal cells.
Specimen part, Treatment
View SamplesTransplanting renal allografts represents the major curative treatment of chronic renal failure. Despite recent advances in immunosuppressive therapy, long-term survival of allografts remains a major clinical problem. Kidney function depends in part on transport proteins such as MRP2 (ABCC2) which facilitates renal secretion of amphiphilic exogenous and endogenous compounds. Inherited variants of genes not related to the immune system have been shown to modify the outcome after renal transplantation. We investigated whether ABCC2 gene variants in the donor kidney affect renal graft function.
Multidrug resistance-related protein 2 genotype of the donor affects kidney graft function.
Sex
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