Microarry datasets for RAW cells stimulated with R848 in the absence or presence of apilimod or API09
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ABSTRACT: Apilimod is a reported TLR pathway antagonist in clinical trial. To understand the mode of action of apilimod, we applied global microarray analysis to explore the effect of apilimod on gene expression of RAW cell in the absence of presence of R848 (TLR7 ligand). RAW cells were stimulated with R848 in the absence or presence of apilimod (1μM). mRNAs were extracted at 0h, 1h,3h, 7h, and 22h for affymetrix analysis. The inactive analog of apilimod (API09) was included as a control.
Project description:Apilimod is a reported TLR pathway antagonist in clinical trial. To understand the mode of action of apilimod, we applied global microarray analysis to explore the effect of apilimod on gene expression of RAW cell in the absence of presence of R848 (TLR7 ligand).
Project description:Compared to wildtype macrophages, IRAK2 deficient macrophages show higher induced gene expression in responsse to CpG B, but not R848 Manuscipt title: The dual function of IRAK2 in TLR9-mediated interfereon and proinflammatory cytokine production Bone marrow derived macrophages from wildtype and IRAK2 knockout mouse were stimulated with CpG B or R848 for 2 hours, or untreated.
Project description:Murine dendritic cells were derived from bone-marrow of 4 mice using GM-CSF. The DC were treated with RNA from gram-positive bacteria Listeria monocytogenes packaged in DOTAP or TLR7 agonist R848. Negative controls were DOTAP with no RNA or mock.
Project description:Samples of monocyte derived dendritic cells (moDCs) from three healthy volunteers untreated and treated with LPS [100ng/ml] or R848 [2.5µg/ml] for different time points (0h,3h,6h,12h and 24h).
Project description:Toll like receptors (TLRs) sense microbial products and initiate adaptive immune responses by activating dendritic cells (DCs). Since pathogens may contain several agonists we asked whether different TLRs may synergize in DC activation. We report that in human and mouse DC TLR3 or TLR4 potently synergize with TLR7, TLR8 or TLR9 in the induction of selected cytokine genes. Upon synergistic stimulation, IL-12, IL-23 and Delta-4 are induced at levels 50-100 fold higher than those induced by optimal concentrations of single agonists, leading to enhanced and sustained TH1 polarizing capacity. Using microarray analysis we show that only 1.5% of the transcripts induced by single TLR agonists are synergistically regulated by combinations of TLR4 and TLR8 agonists.. These results identify a combinatorial code by which DCs discriminate pathogens and provide (suggest) a rationale to design adjuvants for TH1 responses. Series_overall_design: 3 untreated, 3 treated with LPS at 2h, 3 treated with LPS at 8h, 3 treated with R848 at 2h, 3 treated with R848 at 8h, 3 treated with LPS + R848 at 2h, 3 treated with LPS + R848 at 8h
Project description:Gene expression kinetics for BM-DM from C57BL/6 mice challenged by poly(I:C) , R848, poly(I:C)+R848 examined at 6 time points including 0.5, 1, 2, 4, 8, 12 h.
Project description:PCR Array Profiling - R848 does not induce TLR-signaling related genes in TLR7-/- mice. Aim: To corroborate TLR7-dependency of R848 in mice "Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology", Baenziger et al. Blood 2008
Project description:Using RNA-seq, we have reported signaling crosstalk between IFN-α and R848 at the level of transcriptomes highlighting synergsitic gene expression dynamics upon different receptors signaling in microglia cells
Project description:Analysis of whole mouse muscle and inguinal lymph node gene expression signature induced after 6h by in-vivo intramuscularly administration of MF59, alum, CpG, resiquimod (R848), Pam3CSK4 and DMSO and PBS controls. Analysis of splenocyte gene expression signature induced by the same treatments after 6h of incubation. MF59 and alum are licensed human vaccine adjuvants; CpG is a TLR9-agonist adjuvant; resiquimod (R848) is a TLR7/8-agonist adjuvant and Pam3CSK4 is a TLR2-agonist adjuvant.