RNAseq analysis of human CD14+ monocytes exposed to an agonist of Aryl Hydrocarbon Receptor
Ontology highlight
ABSTRACT: Aryl Hydrocarbon Receptor (AhR) is a ligand-activated transcription factor. To understand what genes are controlled by AhR in human monocytes, we performed transcriptomic analysis.
Project description:Immune cells can rapidly adapt their functional program in response to cytokines. How cytokine-induced transcriptional responses are affected by micro-environmental cues remains poorly understood. The Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor sensing environmental signals including metabolites. Here we addressed the cross-talk between Interleukin-4 and AhR signaling in monocytes.
Project description:[original Title] Comparison of expression data of primary murine melanocytes from aryl hydrocarbon deficient mice and corresponding wild-type C57BL/6 mice Melanin is produced exclusively by melanocytes and melanogenesis is the vital response to protect skin cells against Ultraviolet B (UVB)-induced DNA damage. The aryl hydrocarbon receptor (AhR) is a transcription factor, which may be involved in the physiological tanning response. Normal murine melanocytes express functional AhR. We tested gene expression in WT versus AhR-deficient mice primary murine melanocytes, isolated from the skin and cultivated for several passages. Skin epidermal cells from 2 individual C57BL/6 mice and 2 individual AhR-deficient mice (deletion of exon2, AhRtm1Bra) were grown for 6-8 weeks in selection medium to propagate melanocytes.
Project description:We discovered a chemical series that enhances ApoE secretion from human astrocytes through mechanisms independent of LXR agonism. Using chemoproteomics, photoaffinity probes, KINOMEscan analysis, and siRNA knockdowns, we identified the aryl hydrocarbon receptor (AhR), a transcription factor not previously linked to ApoE secretion, as the primary target. AhR antagonism was confirmed to increase ApoE secretion through a panel of agonists/antagonists and genetic knockdown. While chronic AhR inhibition is unsuitable for Alzheimer's treatment due to peripheral effects, these findings highlight AhR as a modulator of ApoE secretion and a pathway worth further exploration. There is two datasets deposited for this project. One dataset was generated through affinity chromatography enrichment, and the second dataset was generated through photo-affinity chromatography enrichment.
Project description:To study the effect of blockade of canonical aryl hydrocarbon receptor (AHR) pathway in human endothelial cells, we treated human umbilical vein endothelial cells (HUVECs) and adipose endothelial cells with a canonical AHR inhibitor, Stemreginin 1 (SR1) and performed bulk RNAseq analysis.
Project description:Acinetobacter baumannii is a highly pathogenic and multidrug-resistant Gram-negative bacterium that causes severe nosocomial infections. To better understand the mechanism of pathogenesis, we compare the proteomes of uninfected and infected human cells, revealing that transcription factor FOS is the host protein most strongly induced by A. baumannii infection. Pharmacological inhibition of FOS reduces the cytotoxicity of A. baumannii in cell-based models, and similar results are also observed in a mouse infection model. A. baumannii outer membrane vesicles (OMVs) are shown to activate the aryl hydrocarbon receptor (AHR) of host cells by inducing the host enzyme tryptophan-2,3-dioxygenase (TDO), producing the ligand kynurenine, which binds AHR. Following ligand binding, AHR is a direct transcriptional activator of the FOS gene. Our results suggest that bacterial infection interacts with host tryptophan metabolism and the transcription factor FOS.
Project description:To study the effect of blockade of canonical aryl hydrocarbon receptor (AHR) pathway in human endothelial cells, we treated human umbilical vein endothelial cells (HUVECs) with a canonical AHR inhibitor, Stemreginin 1 (SR1) and performed bulk RNAseq analysis.
Project description:[original Title] Comparison of expression data of primary murine melanocytes from aryl hydrocarbon deficient mice and corresponding wild-type C57BL/6 mice Melanin is produced exclusively by melanocytes and melanogenesis is the vital response to protect skin cells against Ultraviolet B (UVB)-induced DNA damage. The aryl hydrocarbon receptor (AhR) is a transcription factor, which may be involved in the physiological tanning response. Normal murine melanocytes express functional AhR. We tested gene expression in WT versus AhR-deficient mice primary murine melanocytes, isolated from the skin and cultivated for several passages.
Project description:We report sequencing of chromatin immunoprecipitated DNA (ChIP-Seq) of Aryl Hydrocarbon Receptor (AHR) targets from decidual stromal cells with kynurenine treatment and normal decidualization media