LPS-induced genome-wide RELA binding sites and H3K27ac changes in phraryngeal epithelial cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE132018 | GEO | 2019/06/01
REPOSITORIES: GEO
Similar Datasets
Project description:Gram negative endotoxin Lypopolysaccharide (LPS) leads to a strong innate immune response through TLR4 signalling. This latter pathway activates cannonical NF-kB pathway, including its member RELA. Here, we want to investigate the gene expression response induced by LPS recognition.
2019-06-01 | GSE132019 | GEO
Project description:We report changes in H3K27ac following LPS stimulation in Detroit 562 cells. We were able to identified LPS-increased H3K27ac regions which correlated with RELA binding as well as gene up-regulation. This data set is relevant for airborne bacterial sensing as Detroit 562 cells are nasopharyngeal epithelial cells and LPS is a gram negative bacterial endotoxin.
2018-09-24 | GSE104635 | GEO
Project description:A cyanobacterial LPS antagonist prevents endotoxin shock and blocks sustained TLR4 stimulation required for cytokine expression. We report the identification and biologic characterization of an LPS-like molecule extracted from the cyanobacterium Oscillatoria Planktothrix FP1 (CyP). Keywords: different ligands
2006-07-27 | GSE4748 | GEO
Project description:A cyanobacterial LPS antagonist prevents endotoxin shock and blocks sustained TLR4 stimulation required for cytokine expression. We report the identification and biologic characterization of an LPS-like molecule extracted from the cyanobacterium Oscillatoria Planktothrix FP1 (CyP).
2007-10-26 | E-GEOD-4748 | biostudies-arrayexpress
Project description:Developmental signals are known to modulate inflammation. How ever, the mechanistic insight that links developmental and inflammatory signaling remains elusive. In the current study, we identifya critical role of NF-kB system in mediating stimulus specific crosstalk that allows developmental LTbR signals to sustain inflammatory TLR4 induced RelA/NF-kB response and gene expression. LTbR activated non-canonical signaling targets canonical TLR4 induced, nfkb2 encoded p100 not only to deplete inhibitory IkBd/(p100)2, but also to supplement RelA:p52/NF-kB dimers. Robust crosstalk in the gut epithelial cells are important, as crosstalk-defective nfkb2-/- mice succumbed to gut infection by Citrobacter rodentium due to hypo-inflammatory responses. Finally, we present evidence for a crosstalk motif that integrates tissue microenvironment derived developmental cues to ameliorate the pathogen response. Total RNA from WT early passage MEFs stimulated with ligands LPS, LTbR and LPS+LTbR for 24hrs were analyzed for global gene expression levels
2015-05-01 | E-GEOD-62301 | biostudies-arrayexpress
Project description:Four daily intraperitoneal injections of the Gram-negative bacterial endotoxin lipopolysaccharide (LPS) transiently protects the cerebral cortex against traumatic brain injury. Underlying mechanisms associated with this neuroprotection include increased neuronal production of anti-apoptotic and neurotrophic molecules, microglial-mediated displacement of inhibitory presynaptic terminals innervating the soma of cortical projection neurons, and synchronized firing of cortical projection neurons. The molecular mechanisms responsible for inducing this neuroprotection and microglial activation are unknown. A fundamental question is whether LPS enters the central nervous system (CNS) or mediates it actions on the luminal surface of brain endothelial cells. In this study, we demonstrate that LPS injected into the peritoneum does not enter the CNS or alter tight junctions of brain endothelial cells. However, LPS activation of vascular endothelial cells was substantiated by increased expression of activation markers (CD54 and CD105) and the LPS receptor, TLR4, on CD31-positive brain endothelial cells isolated by flow cytometry. Transcript analyses further revealed significant upregulation of Cxcl10, C3, Ccl2, Il1b, Cxcl2, and Cxcl1 in these activated endothelial cells, consistent with identification of MyD88 as a regulator of these transcripts by pathway analysis. Using conditional brain endothelial gene ablation strategies, we establish that MyD88-dependent endothelial TLR4 signaling and endothelial Cxcl10 expression are essential for LPS-induced neuroprotection and microglial activation. CXCL10 production by brain endothelial cells in response to circulating TLR ligands thus provides a pathway to directly or indirectly signal to CXCR3 on neurons and/or microglia. Targeting activation of brain endothelial receptors provides an attractive and practical approach for inducing transient neuroprotection.
2022-02-01 | GSE193015 | GEO
Project description:Inflammatory response plays an essential role in the resolution of infections. However, inflammation can be detrimental to the organism and cause irreparable damage, for example during sepsis, when a “cytokine storm” can lead to multiple organ failure and often ends in death. One of the strongest triggers of inflammatory response is bacterial lipopolysaccharide (LPS), acting mostly through Toll-like receptor 4 (TLR4). Prior or prolonged exposure to LPS, however, can induce the state of “endotoxin tolerance” where the macrophages and monocytes do not respond to new endotoxin challenge. The cellular mechanisms regulating this phenomenon remain elusive. Our comprehensive secreted protein analysis comparing LPS-tolerant and -responsive monocyte/macrophage-like cells combined with the extracellular flux analysis reveals the robust switch from the inflammatory to metabolic protein expression as well as points to the involvement of specific proteins that may regulate the change from the responsive to the tolerant state
2021-09-09 | PXD021925 | Pride
Project description:Lipid A (a hexaacylated 1,4 bis-phosphate) is a potent immune stimulant for TLR4/MD-2. Upon lipid A ligation, the TLR4/MD-2 complex dimerizes and initiates signal transduction. Historically, studies also suggested the existence of TLR4/MD-2-independent LPS signaling. Here we define the role of TLR4 and MD-2 in LPS signaling by using genome wide expression profiling in TLR4- and MD-2-deficient macrophages after stimulations with peptidoglycan-free LPS and synthetic E.coli lipid A. Of the 1,396 genes found significantly induced or repressed by any one of the treatments in the wildtype macrophages, none was present in the TLR4- or MD-2-deficient macrophages, confirming that the TLR4/MD-2 complex is the only receptor for endotoxin, and are both absolutely required for responses to LPS. Using a molecular genetics approach, we investigated the mechanism of TLR4/MD-2 activation by combining the known crystal structure of TLR4/MD-2 with computer modeling. We used lipid IVa, a defined lipid A mimetic to model the activation of mouse TLR4/MD2. The two phosphates on lipid A were predicted to interact extensively with the two positively charged patches mouse TLR4 according to our dimeric murine TLR4/MD-2/lipid IVa model. These two patches are composed of K263, R337, and K360 (Positive Patch 1), and K367 and R434 (Positive Patch 2). When either Positive Patch was abolished by mutagenesis into Ala, the responses to LPS and lipid A were almost abrogated. Thus, ionic interactions between the two phosphates on lipid A and the two positively charged patches on murine TLR4 appear to be essential for LPS receptor activation.
2011-07-31 | GSE31066 | GEO
Project description:Lipid A (a hexaacylated 1,4 bis-phosphate) is a potent immune stimulant for TLR4/MD-2. Upon lipid A ligation, the TLR4/MD-2 complex dimerizes and initiates signal transduction. Historically, studies also suggested the existence of TLR4/MD-2-independent LPS signaling. Here we define the role of TLR4 and MD-2 in LPS signaling by using genome wide expression profiling in TLR4- and MD-2-deficient macrophages after stimulations with peptidoglycan-free LPS and synthetic E.coli lipid A. Of the 1,396 genes found significantly induced or repressed by any one of the treatments in the wildtype macrophages, none was present in the TLR4- or MD-2-deficient macrophages, confirming that the TLR4/MD-2 complex is the only receptor for endotoxin, and are both absolutely required for responses to LPS. Using a molecular genetics approach, we investigated the mechanism of TLR4/MD-2 activation by combining the known crystal structure of TLR4/MD-2 with computer modeling. We used lipid IVa, a defined lipid A mimetic to model the activation of mouse TLR4/MD2. The two phosphates on lipid A were predicted to interact extensively with the two positively charged patches mouse TLR4 according to our dimeric murine TLR4/MD-2/lipid IVa model. These two patches are composed of K263, R337, and K360 (Positive Patch 1), and K367 and R434 (Positive Patch 2). When either Positive Patch was abolished by mutagenesis into Ala, the responses to LPS and lipid A were almost abrogated. Thus, ionic interactions between the two phosphates on lipid A and the two positively charged patches on murine TLR4 appear to be essential for LPS receptor activation.
2011-07-31 | GSE31067 | GEO
Project description:In endothelial cells (ECs), stimulation of Toll-like receptor 4 (TLR4) by the endotoxin lipopolysaccharide (LPS) induces the release of diverse pro-inflammatory mediators beneficial in controlling bacterial infections. However, their systemic secretion is a main driver of sepsis and chronic inflammatory diseases. Since distinct and rapid TLR4 signaling induction is difficult to achieve by LPS due to its poorly controllable binding and non-specific affinity to other surface molecules and receptors, we engineered new light-oxygen-voltage-sensing (LOV) domain-based optogenetic endothelial cell lines (opto-TLR4-LOV LEC and opto-TLR4-LOV HUVEC) that allow precise temporal and reversible activation of TLR4 signaling pathways. Using quantitative mass spectrometry, RT-qPCR and Western Blot analysis, we show that pro-inflammatory proteins were not only expressed differently, but also had a different time course when the cells were stimulated with light or LPS. Additional functional assays demonstrated that light induction promoted chemotaxis of THP-1 cells, disruption of the EC-monolayer and transmigration. In contrast, ECs incorporating a truncated version of the TLR4 extracellular domain (opto-TLR4 ΔECD2-LOV LEC) revealed high basal activity with fast exploitation of cell signaling system upon illumination. We conclude that the established optogenetic cell lines are well suited to induce rapid and precise photoactivation of TLR4, allowing receptor-specific studies.
2023-05-10 | PXD038764 | Pride