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p(HGNC:TLR4)

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Entity

Name
TLR4
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 4

Tau protein aggregation is associated with cellular senescence in the brain v1.0.0

Inflammasome Involvement in Alzheimer’s Disease v1.0.0

Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer’s disease v1.0.0

Heme Curation v0.0.1-dev

Mechanistic knowledge surrounding heme

In-Edges 25

a(GO:"neurofibrillary tangle") increases p(HGNC:TLR4) View Subject | View Object

NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

a(MESH:Astrocytes) increases p(HGNC:TLR4) View Subject | View Object

Pattern recognition receptors such as the TLR4 receptor are expressed in the brain’s own immune cells like microglia and astrocytes that induce inflammation via cytokine secretion [38]. PubMed:27314526

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Brain
MeSH
Alzheimer Disease
NeuroMMSigDB
Toll like receptor subgraph

a(MESH:Microglia) increases p(HGNC:TLR4) View Subject | View Object

Pattern recognition receptors such as the TLR4 receptor are expressed in the brain’s own immune cells like microglia and astrocytes that induce inflammation via cytokine secretion [38]. PubMed:27314526

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Brain
MeSH
Alzheimer Disease
NeuroMMSigDB
Toll like receptor subgraph

a(CHEBI:genistein) decreases p(HGNC:TLR4) View Subject | View Object

Pretreatment with genistein significantly alleviated A 25-35-stimulated TLR4 and NF-B expres-sion, DNA binding and NF-B activities[159]. PubMed:29179999

Appears in Networks:

a(PUBCHEM:441923) decreases p(HGNC:TLR4) View Subject | View Object

The expression of the protein and mRNA of TLR3, TLR4, NF-B and TNF receptor associated factor 6 (TRAF-6) were substantially decreased by ginsenoside Rg1, and it also decreased the expression of TNF- and IFN- [227] PubMed:29179999

Appears in Networks:

a(CHEBI:heme) increases p(HGNC:TLR4) View Subject | View Object

The TLR4 activates two distinct pathways: MyD88 and TRIF. In macrophages, heme induces a biased MyD88 activation and the secretion of the pro-inflammatory cytokines TNF and KC. PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:heme) increases p(HGNC:TLR4) View Subject | View Object

Moreover, human embryonic kidney (HEK) cells transfected with human TLR4 secretes IL-8 upon stimulation with heme (Piazza et al., 2011). PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:heme) increases p(HGNC:TLR4) View Subject | View Object

Heme amplifies cytokines induced by cell surface receptors (TLR2, TLR4, TLR5), endosome receptors (TLR3, TLR9), and cytosolic receptors (NOD1 and NOD2). PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:heme) increases p(HGNC:TLR4) View Subject | View Object

In fact, TLR4 is involved in intracerebral hemorrhage (ICH) induced by heme (Lin et al., 2012). PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

a(CHEBI:heme) positiveCorrelation p(HGNC:TLR4) View Subject | View Object

Other studies demonstrated that heme can trigger the activation of Toll-like receptor 4 and inflammasomes, thus leading to inflammatory reactions.5,35–37 PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney
Text Location
Discussion

a(CHEBI:heme) increases p(HGNC:TLR4) View Subject | View Object

Most studies concerning the pathophysiological roles of heme have focused on the protective effect of the heme-degrading enzyme, heme oxygenase 1 (HO-1) [25] (Box 2), and on the effect of this danger-associated molecule on cells, leading to oxidative stress, TLR4 signaling [26,27], and NLRP3 inflammasome activation [28] (Box 4). PubMed:26875449

Appears in Networks:
Annotations
Text Location
Review

a(CHEBI:heme) positiveCorrelation p(HGNC:TLR4) View Subject | View Object

Cell-free heme selectively triggers pro-inflammatory receptors such as TLR-4 and BACH-1, and activates proteasomes25. PubMed:27515135

Appears in Networks:
Annotations
Text Location
Introduction

a(CHEBI:heme) increases act(p(HGNC:TLR4)) View Subject | View Object

Purified heme was found to be an activator of TLR4 8,11,27 in some studies and of the inflammasome 9 in others, and these activities were considered to be the molecular mechanism behind the coexistence of inflammation and hemolysis. PubMed:29610666

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Mitochondria
Text Location
Discussion

a(CHEBI:heme) increases p(HGNC:TLR4) View Subject | View Object

Only under protein-free conditions did we observe a limited heme-induced TNF-alpha response in cultured macrophages, which was triggered via signaling of the classical TLR4–MyD88–TRIF pathway of NF-kB activation.28 PubMed:29610666

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Mitochondria
Text Location
Discussion

a(CHEBI:heme) positiveCorrelation act(p(HGNC:TLR4)) View Subject | View Object

The released heme can activate the innate immune pattern recognition receptor toll-like receptor 4 (TLR4) on inflammatory cells, platelets and endothelium, promoting a pro-inflammatory and pro-coagulant phenotype, ultimately leading to vaso-occlusion, ischemia-reperfusion physiology, tissue injury, and pain in murine models of SCD [5, 7±10]. PubMed:29694434

Appears in Networks:
Annotations
MeSH
Blood Platelets
MeSH
Anemia, Sickle Cell
Text Location
Introduction

a(CHEBI:heme) increases p(HGNC:TLR4) View Subject | View Object

Heme released from cell-free hemoglobin has been described to be an activator of TLR-4 [39, 41, 42]. PubMed:29956069

Appears in Networks:
Annotations
MeSH
Arteries
MeSH
Sepsis
Text Location
Review

a(CHEBI:heme) increases p(HGNC:TLR4) View Subject | View Object

Heme/TLR-4 signaling, moreover, was found to activate NF-κB and trigger vaso-occlusion [42]. PubMed:29956069

Appears in Networks:
Annotations
MeSH
Arteries
MeSH
Sepsis
Text Location
Review

a(CHEBI:heme) increases p(HGNC:TLR4) View Subject | View Object

In mice, this response was attenuated after administration of the TLR-4 inhibitor, TAK-242, suggesting hemin potentiates pulmonary macrophage activation and inflammation through hemin-induced TLR-4 receptor binding [27]. PubMed:30281034

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

a(HM:"Pathogen Associated Molecular Pattern") increases act(p(HGNC:TLR4)) View Subject | View Object

The cause of sepsis is primarily an exaggerated, generalized inflammatory response to an extrinsic stimulus. Mechanistically, so-called PAMPs (pathogen-associated molecular patterns) lead to the activation of pattern recognition receptors (PRRs) such as tolllike receptors (TLRs) and C-type lectin receptors (CLRs) [28, 29]. PubMed:29956069

Appears in Networks:
Annotations
MeSH
Sepsis
Text Location
Review

a(MESH:Alarmins) increases act(p(HGNC:TLR4)) View Subject | View Object

In recent years, it has also been shown that toll-like receptors and other pattern recognition receptors are activated not only by extrinsic factors but also by intrinsic stimuli (so called damage-associated molecular patterns, DAMPs) that are released when the host cell is damaged [27, 29]. PubMed:29956069

Appears in Networks:
Annotations
MeSH
Arteries
MeSH
Sepsis
Text Location
Review

bp(GO:"inflammatory response") positiveCorrelation p(HGNC:TLR4) View Subject | View Object

Other studies demonstrated that heme can trigger the activation of Toll-like receptor 4 and inflammasomes, thus leading to inflammatory reactions.5,35–37 PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney
Text Location
Discussion

bp(GO:"inflammatory response") positiveCorrelation act(p(HGNC:TLR4)) View Subject | View Object

The released heme can activate the innate immune pattern recognition receptor toll-like receptor 4 (TLR4) on inflammatory cells, platelets and endothelium, promoting a pro-inflammatory and pro-coagulant phenotype, ultimately leading to vaso-occlusion, ischemia-reperfusion physiology, tissue injury, and pain in murine models of SCD [5, 7±10]. PubMed:29694434

Appears in Networks:
Annotations
MeSH
Blood Platelets
MeSH
Anemia, Sickle Cell
Text Location
Introduction

complex(a(CHEBI:lipopolysaccharide), p(HGNC:TLR4)) hasComponent p(HGNC:TLR4) View Subject | View Object

Appears in Networks:

path(MESH:"Brain Edema") positiveCorrelation p(HGNC:TLR4) View Subject | View Object

In fact, Tlr4-/- or anti-TLR4 treatment suppresses heme-induced neuroinflammation, edema, and neurologic deficit. PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

path(MESH:"Neurogenic Inflammation") positiveCorrelation p(HGNC:TLR4) View Subject | View Object

In fact, Tlr4-/- or anti-TLR4 treatment suppresses heme-induced neuroinflammation, edema, and neurologic deficit. PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

Out-Edges 17

p(HGNC:TLR4) increases bp(GO:"cytokine secretion") View Subject | View Object

Pattern recognition receptors such as the TLR4 receptor are expressed in the brain’s own immune cells like microglia and astrocytes that induce inflammation via cytokine secretion [38]. PubMed:27314526

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Brain
MeSH
Alzheimer Disease
NeuroMMSigDB
Toll like receptor subgraph

p(HGNC:TLR4) increases p(HGNC:MYD88) View Subject | View Object

Moreover, human embryonic kidney (HEK) cells transfected with human TLR4 secretes IL-8 upon stimulation with heme (Piazza et al., 2011). PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:TLR4) increases p(HGNC:MYD88) View Subject | View Object

The TLR4 activates two distinct pathways: MyD88 and TRIF. In macrophages, heme induces a biased MyD88 activation and the secretion of the pro-inflammatory cytokines TNF and KC. PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:TLR4) increases p(HGNC:MYD88) View Subject | View Object

Only under protein-free conditions did we observe a limited heme-induced TNF-alpha response in cultured macrophages, which was triggered via signaling of the classical TLR4–MyD88–TRIF pathway of NF-kB activation.28 PubMed:29610666

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Mitochondria
Text Location
Discussion

p(HGNC:TLR4) increases p(HGNC:TICAM1) View Subject | View Object

The TLR4 activates two distinct pathways: MyD88 and TRIF. In macrophages, heme induces a biased MyD88 activation and the secretion of the pro-inflammatory cytokines TNF and KC. PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:TLR4) increases p(HGNC:TICAM1) View Subject | View Object

Only under protein-free conditions did we observe a limited heme-induced TNF-alpha response in cultured macrophages, which was triggered via signaling of the classical TLR4–MyD88–TRIF pathway of NF-kB activation.28 PubMed:29610666

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Mitochondria
Text Location
Discussion

p(HGNC:TLR4) increases complex(p(HGNC:MAPK1), p(HGNC:MAPK14), p(HGNC:MAPK8)) View Subject | View Object

TLR4 activation leads to MAPKs and NFκB activation, which are necessary to TNF secretion. PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:TLR4) increases p(HGNC:NFKB1) View Subject | View Object

TLR4 activation leads to MAPKs and NFκB activation, which are necessary to TNF secretion. PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
leukocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

p(HGNC:TLR4) positiveCorrelation path(MESH:"Neurogenic Inflammation") View Subject | View Object

In fact, Tlr4-/- or anti-TLR4 treatment suppresses heme-induced neuroinflammation, edema, and neurologic deficit. PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

p(HGNC:TLR4) positiveCorrelation path(MESH:"Brain Edema") View Subject | View Object

In fact, Tlr4-/- or anti-TLR4 treatment suppresses heme-induced neuroinflammation, edema, and neurologic deficit. PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

p(HGNC:TLR4) increases path(MESH:Atherosclerosis) View Subject | View Object

Indeed, TLRs and NLRP3 have been associated with atherosclerosis development. PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Cerebral Hemorrhage
Text Location
Review

p(HGNC:TLR4) increases p(HGNC:TNF) View Subject | View Object

Haem also induces tumour necrosis factor (TNF) secretion in monocyte/macrophages through TLR4 and the adaptor molecule, MYD88 (Figueiredo et al, 2007). PubMed:25307023

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

p(HGNC:TLR4) positiveCorrelation a(CHEBI:heme) View Subject | View Object

Other studies demonstrated that heme can trigger the activation of Toll-like receptor 4 and inflammasomes, thus leading to inflammatory reactions.5,35–37 PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney
Text Location
Discussion

p(HGNC:TLR4) positiveCorrelation a(CHEBI:heme) View Subject | View Object

Cell-free heme selectively triggers pro-inflammatory receptors such as TLR-4 and BACH-1, and activates proteasomes25. PubMed:27515135

Appears in Networks:
Annotations
Text Location
Introduction

act(p(HGNC:TLR4)) positiveCorrelation a(CHEBI:heme) View Subject | View Object

The released heme can activate the innate immune pattern recognition receptor toll-like receptor 4 (TLR4) on inflammatory cells, platelets and endothelium, promoting a pro-inflammatory and pro-coagulant phenotype, ultimately leading to vaso-occlusion, ischemia-reperfusion physiology, tissue injury, and pain in murine models of SCD [5, 7±10]. PubMed:29694434

Appears in Networks:
Annotations
MeSH
Blood Platelets
MeSH
Anemia, Sickle Cell
Text Location
Introduction

p(HGNC:TLR4) positiveCorrelation bp(GO:"inflammatory response") View Subject | View Object

Other studies demonstrated that heme can trigger the activation of Toll-like receptor 4 and inflammasomes, thus leading to inflammatory reactions.5,35–37 PubMed:26794659

Appears in Networks:
Annotations
Cell Ontology (CL)
epithelial cell
MeSH
Kidney
Text Location
Discussion

act(p(HGNC:TLR4)) positiveCorrelation bp(GO:"inflammatory response") View Subject | View Object

The released heme can activate the innate immune pattern recognition receptor toll-like receptor 4 (TLR4) on inflammatory cells, platelets and endothelium, promoting a pro-inflammatory and pro-coagulant phenotype, ultimately leading to vaso-occlusion, ischemia-reperfusion physiology, tissue injury, and pain in murine models of SCD [5, 7±10]. PubMed:29694434

Appears in Networks:
Annotations
MeSH
Blood Platelets
MeSH
Anemia, Sickle Cell
Text Location
Introduction

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.