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The adjuvant combination of dmLT and MPL-A activates the canonical, non-pyroptotic NLRP3 inflammasome in dendritic cells

ABSTRACT: The purpose if this experiment was to determine how a 24 hour treatment with dmLT, MPL-A, and the combination thereof induced gene expression in dendritic cells when compared to LPS and ATP treatment. The knowledge gained from this study would allow us to identify mechanistic pathways that are unique to each adjuvant, which would allow us to further explore their function in DCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE227294 | GEO | 2023/03/15

REPOSITORIES: GEO

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Transcription profiling of mouse spleen after immunized using LPS vs MPL as adjuvant.

Project description:An unresolved issue in immunology is the extent to which inflammatory effects are needed for robust T cell responses. In this study, mice were immunized by iv injection using either high toxicity lipopolysaccharide (LPS) or low toxicity monophosphoryl lipid A (MPL) as adjuvant. Six hours after iv immunization, whole spleens were harvested and gene expression was measured in unfractionated splenic populations of cells. The analysis indicated that the low toxicity adjuvanticity of MPL was associated with TLR4-mediated signaling that was biased to the TRIF branch of TLR4, while LPS generated balanced MyD88 and TRIF-associated outcomes. Experiment Overall Design: B6.SJL mice adoptively transferred with T cells from B6.OTI and OTII transgenic TCR transgenic were immunized via intravenous injection with ova peptides alone ("Ova"), or with LPS ("OvaLPS") or MPL as adjuvant ("OvaMPL"). Six hours after immunization, the mice were euthanized by cervical dislocation, the spleens were removed and immediately lysed in guanidium chloride, and kept frozen until being used to extract total cellular RNA. Three mice each were given the indicated treatments, with independent processing and analysis of nine samples total.

2008-06-15 | E-GEOD-7768 | biostudies-arrayexpress

Expression data from spleens of mice immunized using LPS vs MPL as adjuvant.

2007-06-09 | GSE7768 | GEO

Gene therapy of Mpl -/- mouse LSK cells

Project description:Comparison of Mpl-/- mouse LSK cells, either treated with control (GFP) or Mpl lentivirus. Lineage negative bone marrow cells were isolated and transduced and transplanted into Mpl-/- recipient mice. After transplantation and follow up mice were sacrificed and LSK (lineage negative, Sca-1 positive, cKit positive) cells were isolated by FACS. RNA was isolated using RNeasy Micro Kit (Qiagen GmbH, Hilden, Germany) and RNA was amplified for microarray hybridization using the Nugen Ovation system (Nugen Technologies, AC Bemmel, Netherlands). The resulting material was hybridized to Affymetrix Mouse 430 2.0 arrays. RMA normalization and summarization was performed in R 2.10 using Bioconductor packages. The aim was to show the normalization of Mpl associated gene expression. 3 control (GFP transduced) samples of Mpl -/- mouse LSK cells and 3 treatment (Mpl transduced) samples of Mpl -/- mouse LSK cells.

2011-01-03 | E-GEOD-26403 | biostudies-arrayexpress

Mercury and arsenic attenuate canonical and non-canonical NLRP3 inflammasome activation.

Project description: Not available

| S-EPMC6135747 | biostudies-literature

Gene therapy of Mpl -/- mouse LSK cells

2011-01-03 | GSE26403 | GEO

Canonical Nlrp3 inflammasome activation links systemic age-related inflammation with functional decline

Project description:This experiment was performed to analyze the contribution of NLRP3 inflammasome activation to age-related changes in hippocampal RNA. The hypothesis was that decreased inflammasome activation would reduce hippocampal inflammation. Results indicate that inflammasome knockout animals are protected from age-related changes in hippocampal gene expression Gene expression profiles of young (1 month) and old (21-23 month) wild type, CIAS -/- and ASC -/- mouse hippocampal tissue were compared. Total mRNA was extracted using Trizol.

2013-09-05 | E-GEOD-43034 | biostudies-arrayexpress

RNA-SEQ Quantitative Analysis of WT and Mpl-del-overexpressing AMKL cell Transcriptomes

Project description:In the previous studies, we reported that Mpl alternative splicing form Mpl-del overexpressed in acute megakaryoblasttic leukemia (AMKL) patients and mediated thrombopoietin signaling to promote AMKL cells malignant proliferation and chemotherapy resisitance. To investigate the detailed mechanism of Mpl-del mediated AMKL cells proliferation and survival, the AMKL cell Dami stably expressing GFP or Mpl-del-GFP were established by transduction with GFP or Mpl-del-GFP lentiviruses and treated with 20ng/ml TPO for RNA-SEQ analysis to examine the expression of proliferation and survival-related genes. Our results indicated that the levels of the "leading edge" genes that account for survival and prolieration were significantly higher in Mpl--del overexpressed AMKL cells.

2019-04-04 | GSE127762 | GEO

Endocytosis of the thrombopoietin receptor Mpl regulates megakaryocyte and erythroid maturation in mice

Project description:Dnm2fl/fl Pf4-Cre (Dnm2Plt-/-) mice lacking the endocytic GTPase dynamin 2 (DNM2) in platelets and megakaryocytes (MKs) develop hallmarks of myelofibrosis. At the cellular level, the tyrosine kinase JAK2 is constitutively active but decreased in expression in Dnm2Plt-/- platelets. Additionally, Dnm2Plt-/- platelets cannot endocytose the thrombopoietin (TPO) receptor Mpl, leading to elevated circulating TPO levels. Here, we assessed whether the hyperproliferative phenotype of Dnm2Plt-/- mice was due to JAK2 constitutive activation or elevated circulating TPO levels. In unstimulated Dnm2Plt-/- platelets, STAT3 and to a lower extent STAT5 were phosphorylated, but their phosphorylation was slowed and diminished upon TPO stimulation. We further crossed Dnm2Plt-/- mice in the Mpl-/- background to generate Mpl-/- Dnm2Plt-/- mice lacking Mpl ubiquitously and DNM2 in platelets and MKs. Mpl-/- Dnm2Plt-/- platelets had severely reduced JAK2 and STAT3 but normal STAT5 expression. Mpl-/- Dnm2Plt-/- mice had severely reduced bone marrow MK and hematopoietic stem and progenitor cell numbers. Additionally, Mpl-/- Dnm2Plt-/- mice had severe erythroblast maturation defects, decreased expression of hemoglobin and heme homeostasis genes, increased expression of ribosome biogenesis and protein translation genes, and developed anemia with grossly elevated plasma erythropoietin levels, leading to early fatality by postnatal day 25. Mpl-/- Dnm2Plt+/+ mice had impaired EB development at three weeks of age, which normalized with adulthood. Together, the data shows that DNM2-dependent Mpl-mediated endocytosis in platelets and MKs is required for steady-state hematopoiesis and provides novel insights into a developmentally controlled role for Mpl in normal erythropoiesis, regulating hemoglobin and heme production.

2022-08-25 | GSE206343 | GEO

Adjuvant Secretomes - Adjuvant-induced human monocyte secretome profiles reveal adjuvant- and age-specific protein signatures

Project description:Adjuvant-induced human monocyte secretome profiles reveal adjuvant- and age-specific protein signatures.

2016-03-14 | PXD003534 | Pride

Comparative tissue proteomics reveals unique action mechanisms of vaccine adjuvants

Project description:This proteomics data are generated from mouse skin treated with physical radiofrequency adjuvant and common chemical adjuvants, such as AddaVax, MPL, Alum, MPL/Alum.

2022-11-09 | MSV000090681 | MassIVE

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