Mus musculus
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ABSTRACT:
PROVIDER: PRJNA102541 | ENA |
REPOSITORIES: ENA
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Project description:IRAK-4 is an essential component of the signal transduction complex downstream of the IL-1- and Toll-like receptors. Though regarded as the first kinase in the signaling cascade, the role of IRAK-4 kinase activity versus its scaffold function is still controversial. In order to investigate the role of IRAK-4 kinase function in vivo, âknock-inâ mice were generated by replacing the wild type IRAK-4 gene with a mutant gene encoding kinase deficient IRAK-4 protein (IRAK-4 KD). Analysis of bone marrow macrophages obtained from WT and IRAK-4 KD mice with a number of experimental techniques demonstrated that the IRAK-4 KD cells greatly lack responsiveness to stimulation with the Toll-like receptor 4 (TLR4) agonist LPS. One of the techniques used, microarray analysis, identified IRAK-4 kinase-dependent LPS response genes and revealed that the induction of LPS-responsive mRNAs was largely ablated in IRAK-4 KD cells. In summary, our results suggest that IRAK-4 kinase activity plays a critical role in TLR4-mediated induction of inflammatory responses. Experiment Overall Design: The response of mouse bone marrow macrophages from WT and IRAK4 kinase dead animals to stimulation with LPS at two time points was determined. There were 12 samples in total, 6 from WT and 6 from IRAK4 kinase dead cells; for each strain there were 3 conditions: growth for 4 hours without stimulation (the strain-specific control), growth for 1 hour with stimulation, and growth for 4 hours with stimulation; for each condition there were two biological replicates.
2008-10-20 | E-GEOD-9037 | biostudies-arrayexpress
Project description:IRAK-4 is an essential component of the signal transduction complex downstream of the IL-1- and Toll-like receptors. Though regarded as the first kinase in the signaling cascade, the role of IRAK-4 kinase activity versus its scaffold function is still controversial. In order to investigate the role of IRAK-4 kinase function in vivo, knock-in mice were generated by replacing the wild type IRAK-4 gene with a mutant gene encoding kinase deficient IRAK-4 protein (IRAK-4 KD). Analysis of embryonic fibroblasts and macrophages obtained from IRAK-4 KD mice with a number of experimental techniques demonstrated that they greatly lack responsiveness to stimulation with IL-1b or a Toll-like receptor 7 (TLR7) agonist. One of the techniques used, microarray analysis, identified IRAK-4 kinase-dependent IL-1b response genes in mouse embryonic fibroblasts and revealed that the induction of IL-1b-responsive mRNAs was largely ablated in IRAK-4 KD cells. In summary, our results suggest that IRAK-4 kinase activity plays a critical role in IL-1R/TLR7-mediated induction of inflammatory responses. Experiment Overall Design: The response of mouse embryonic fibroblasts from WT and IRAK4 kinase dead animals to stimulation with IL-1b at two time points was determined. There were 12 samples in total, 6 from WT and 6 from IRAK4 kinase dead cells; for each strain there were 3 conditions: growth for 4 hours without stimulation (the strain-specific control), growth for 1 hour with stimulation, and growth for 4 hours with stimulation; for each condition there were two biological replicates.
2007-11-15 | E-GEOD-6789 | biostudies-arrayexpress
Project description:Exciting discoveries related to IL-1R/TLR signaling in development of atherosclerosis plaque have triggered intense interest in the molecular mechanisms by which innate immune signaling modulates the onset and development of atherosclerosis. Previous studies have clearly shown the definitive role of proinflammatory cytokine IL-1 in the development of atherosclerosis. Recent studies have provided direct evidence supporting a link between innate immunity and atherogenesis. While it is still controversial about whether infectious pathogens contribute to cardiovascular diseases, direct genetic evidence indicates the importance of IL-1R/TLR signaling in atherogenesis. In this study, we examined the role of IRAK4 kinase activity in modified LDL-mediated signaling using bone marrow-derived macrophage as well as in vivo model of atherosclerosis. First, we found that the IRAK4 kinase activity was required for modified LDL-induced NFκB activation and expression of a subset of proinflammatory genes, but not for the activation of MAPKs in bonemarrow-derived macrophage. IRAK4 kinase inactive knock-in (IRAK4KI) mice were bred onto ApoE-/- mice to generate IRAK4KI/ApoE-/- mice. Importantly, the aortic sinus lesion formation was impaired in IRAK4KI/ApoE-/- mice compared to that in ApoE-/- mice. Furthermore, proinflammatory cytokine production was reduced in the aortic sinus region of IRAK4KI/ApoE-/- mice compared to that in ApoE-/- mice. Taken together, our results indicate that the IRAK4 kinase plays an important role in modified LDL-mediated signaling and the development of atherosclerosis, suggesting that pharmacological inhibition of IRAK4 kinase activity might be a feasible approach in the development of anti-atherosclerosis drugs. To identify global changes in gene expression, we examined gene expression profiles of macrophages from wild-type and IRAK4 kinase-inactive knock-in mice in response to acLDL stimulation using the Illumina microarray with probes for 23,000 transcripts. Bone marrow-derived macrophages from wild-type and IRAK4 kinase-inactive knock-in mice were treated with acLDL for 24 hours.
2010-10-23 | E-GEOD-24894 | biostudies-arrayexpress
Project description:response to IL-1b of WT and IRAK4 kinase dead mouse embryonic fibroblasts
| PRJNA99223 | ENA
Project description:Gene level expression estimate using the Whole Transcript (WT) Assay approach of the Gene 1.0 ST Array System for Mouse. This assay was done to identify the RIPK1-dependent gene expression changes in mouse BMDMs. Cost-effective gene-level analysis based on whole-transcript coverage. We analyzed Bone Marrow Derived Macrophages (BMDMs) under 4 different conditions (Control, LPS, LPS/zVAD, LPS/zVAD/Nec-1) to assess inflammatory changes in RIPK1 kinase dependent manner compared to LPS, LPS/zVAD plus RIPK1 inhibitor Nec-1 and control.
2016-09-07 | E-GEOD-72797 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE16180: Bone-marrow derived macrophages response to the Whipple's disease agent, Tropheryma whipplei GSE20207: Wild-type bone-marrow derived macrophages response to Escherichia coli lipopolysaccharide (LPS) GSE20208: Interleukin-16-knock-out bone-marrow derived macrophages response to Escherichia coli lipopolysaccharide (LPS) GSE20209: Interleukin-16-knock-out bone-marrow derived macrophages response to the Whipple's disease agent, Tropheryma whipplei Refer to individual Series
2010-11-08 | E-GEOD-20210 | biostudies-arrayexpress
Project description:Gene expression in bone marrow-derived macrophages (BMDMs) from WT and mice lacking the transcriptional repressor Kruppel-like factor 3 (KLF3). We cultured BMDMs from bone marrow for 7-10 days then treated cells with 100 ng/mL lipopolysaccharide (LPS) or vehicle (PBS) for 0 h or 8 h, followed by RNA extraction. We aimed to investigate deregulated genes and pathways in macrophages lacking KLF3, during the inflammatory response to endotoxin (LPS).
2020-03-24 | GSE121646 | GEO
Project description:Purpose: The goal of this study is to compare downstream genes of Sema6D signaling in LPS plus IFNg stimulated macrophages. Methods: Bone marrow derived macrophage mRNA profiles of 7 weeks of wild type (WT) and Sema6D-/- mice were stimulated by LPS for 4 hrs. Results: According to this comparison, we found that 550 genes were downregulated in Sema6D-/- macrophages than WT macrophages in response to LPS. Conclusions: Our study represents 62 genes were supressed in both M1 and M2 Sema6D-/- macrophage than WT macrophages, suggesting of Sema6D reverse sigaling genes.
2018-05-20 | GSE99047 | GEO
Project description:Expression profiles of GRdim mutant macrophages (mouse, bone-marrow derived) treated with LPS for 6 hrs or with LPS (6hrs) + Dex (O/N 1uM). Identification of GR-regulated genes in response to LPS.
2015-04-23 | GSE68160 | GEO
Project description:Expression profiles of GRdim mutant macrophages (mouse, bone-marrow derived) treated with LPS for 6 hrs or with LPS (6hrs) + Dex (O/N 1uM). Identification of GR-regulated genes in response to LPS. 3 Grdim mutant macrophages samples treated with LPS (6hrs) and 3 Grdim mutant macrophage samples treated with LPS (6hrs) and Dex (overnight).
2015-04-23 | E-GEOD-68160 | biostudies-arrayexpress