The role of Ch25h in the macrophage response to poly(I:C)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Aderem Lab
PROVIDER: E-GEOD-54064 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Cross-talk between sterol regulatory pathways and inflammatory pathways has been demonstrated to play an important role in the response to viral infections. 25-Hydroxycholesterol (25HC) is an oxysterol that plays multiple roles in lipid biosynthesis and immunity, and has recently been shown to have anti-viral activity. Surprisingly, we found that deletion of Ch25h, the gene encoding the enzyme responsible for 25HC production, is protective in a mouse model of influenza infection as a result of decreased inflammatory-induced pathology. Anti-viral responses involve complex gene regulatory circuits with multiple feedback loops and we demonstrated that 25HC acts as an amplifier of TLR3 signaling in macrophages and airway epithelial cells. We determined that 25HC amplifies TLR3 signaling, at least in part, by mediating the up-regulation and recruitment of the AP1 components Fos and Jun to the promoters of a subset of TLR3 responsive genes. Thus, our study demonstrates for the first time that in addition to its direct anti-viral role, 25HC also regulates transcriptional responses and acts as an amplifier of TLR3-induced inflammation via AP1. 14 RNA samples from murine Let1a cells (immortalized airway epithelial cells) were analyzed using Agilent microarrays. Cells from C57BL/6 and Ch25h-/- mice were analyzed after mock stimulation or stimulation with 6ug/mL poly(I:C) or 5μM 25-Hydroxycholesterol for 6 or 18 hours. For each condition, two biological replicates were analyzed.
2014-06-20 | E-GEOD-54063 | biostudies-arrayexpress
Project description:Cross-talk between sterol regulatory pathways and inflammatory pathways has been demonstrated to play an important role in the response to viral infections. 25-Hydroxycholesterol (25HC) is an oxysterol that plays multiple roles in lipid biosynthesis and immunity, and has recently been shown to have anti-viral activity. Surprisingly, we found that deletion of Ch25h, the gene encoding the enzyme responsible for 25HC production, is protective in a mouse model of influenza infection as a result of decreased inflammatory-induced pathology. Anti-viral responses involve complex gene regulatory circuits with multiple feedback loops and we demonstrated that 25HC acts as an amplifier of TLR3 signaling in macrophages and airway epithelial cells. We determined that 25HC amplifies TLR3 signaling, at least in part, by mediating the up-regulation and recruitment of the AP1 components Fos and Jun to the promoters of a subset of TLR3 responsive genes. Thus, our study demonstrates for the first time that in addition to its direct anti-viral role, 25HC also regulates transcriptional responses and acts as an amplifier of TLR3-induced inflammation via AP1. 24 RNA samples from murine bone-marrow-derived macrophages were analyzed using Agilent microarrays. Macrophages from C57BL/6 and Ch25h-/- mice were analyzed after mock stimulation or stimulation with 6ug/mL poly(I:C) or for 6 or 18 hours. For each condition, three biological replicates (macrophages derived from independent mice) were analyzed.
2014-06-20 | E-GEOD-54062 | biostudies-arrayexpress
Project description:Our systems analysis reported here demonstrates that TLR-responses in macrophages are markedly impaired by SHARPIN deficiency, and that SHARPIN controls expression of a subset of TLR2-induced, NF-kB and AP-1 dependent genes that overlaps with those affected by the hypomorphic panr2 mutation in NEMO. 46 total RNA samples from murine bone marrow derived macrophages were analyzed (32 by Agilent array, 14 by Affymetrix Exon array) On Agilent array, the responses of macrophages to 12hr stimulation with the TLR2 ligand PAM3CSK4 (300ng/mL) were analyzed in biological duplicates for five mutant mouse strains and respective controls: Sharpin(cpdm), Ikbkg(panr2), Atf3(KO), Il10(KO), and Nfkb1(KO).
2011-08-30 | E-GEOD-29888 | biostudies-arrayexpress
Project description:Our systems analysis reported here demonstrates that TLR-responses in macrophages are markedly impaired by SHARPIN deficiency, and that SHARPIN controls expression of a subset of TLR2-induced, NF-kB and AP-1 dependent genes that overlaps with those affected by the hypomorphic panr2 mutation in NEMO. 46 total RNA samples from murine bone marrow derived macrophages were analyzed (32 by Agilent array, 14 by Affymetrix Exon array) On Affymetrix Exon array, the responses of macrophages to 12hr stimulation with the TLR2 ligand PAM3CSK4 (300ng/mL) were analyzed in biological duplicates for the Map3k8(sluggish) mutant and respective controls and in singlet for the Tnf(KO) mutant compared to two respective WT controls.
2011-08-30 | E-GEOD-29891 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE29888: Systems analysis identifies an essential role for SHARPIN in macrophage TLR2 responses (Agilent) GSE29891: Systems analysis identifies an essential role for SHARPIN in macrophage TLR2 responses (Affymetrix) Refer to individual Series
2011-08-30 | E-GEOD-29947 | biostudies-arrayexpress
Project description:The concentrations and copy number of proteins in the mouse Bone Marrow Derived proteome was determined for control, 10 ng/mL LPS stimulation, and LPS stimulation plus the addition of 100 nM dexamethasone, after an incubation for 24 hours and with four biological replicates for each condition. Over 6000 proteins were detected, 410 of which were upregulated by LPS (> 1.5-fold increase, adjusted p value < 0.05). 125 of these LPS-induced proteins were significantly regulated by Dexamethason > 1.5 fold 899 increase or decrease, adjusted p value <0.05).
2024-01-26 | PXD041375 | Pride
Project description:Gene expression of LSK (lin-Sca-Kit+) hematopoietic stem cells from wild type mice was compared with LSK from Cebpa knock-in mutant mice (K/K, K/L, and L/L mutants). Fetal liver cells for each genotype were competitively transplanted into irradiant recipients. Donor-derived LSK cells were isolated by FACS sorting of recipient bone marrow. 3 biological replicates of each were generated and expression profiles were determined by hybridization to Affymetrix Moe430_2 arrays.
2009-11-03 | E-TABM-695 | biostudies-arrayexpress
Project description:In this study we have analysed the regulation of miRNA in bone marrow derived macrophages in response to the fungal pathogen heat killed Candida albicans and bacterial cell wall component, LPS. The aim of the study was to identify and validate miRNAs involved in the innate immune system in response to fungal and bacterial stimuli and investigate potential mechanisms for their transcription. Three mice were used as 3 biological replicates. The bone marow derived macrophages from each mouse were divided into two and either left untreated or were stimulatred for 16 h with heat killed Candida albicans.
2010-12-31 | E-GEOD-21970 | biostudies-arrayexpress
Project description:Gene expression of LT-HSC (CD150+Flt3-lin-Sca-Kit+) hematopoietic stem cells from wild type mice was compared with LT-HSC from Cebpa knock-in mutant mice (K/L mutants). Fetal liver cells for each genotype were competitively transplanted into irradiant recipients. Donor-derived LT-HSC cells were isolated by FACS sorting of recipient bone marrow. Biological replicates of each (3 for wt, 2 for K/L) were generated and expression profiles were determined by hybridization to Affymetrix Moe430_2 arrays.
2009-11-03 | E-TABM-694 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-12-22 | E-GEOD-52773 | biostudies-arrayexpress