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path(MESH:Inflammation)

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Entity

Name
Inflammation
Namespace
mesh
Namespace Version
20180828
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/1b20f0637c395f8aa89c2e2e342d7b704062c242/external/mesh-names.belns

Appears in Networks 12

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Activity-dependent neuroprotective protein deficiency models synaptic and developmental phenotypes of autism-like syndrome v1.0.0

Heme Curation v0.0.1-dev

Mechanistic knowledge surrounding heme

In-Edges 83

act(a(MESH:"Lymphatic Vessels")) negativeCorrelation path(MESH:Inflammation) View Subject | View Object

Analysis of lymphoid and myeloid cell populations in the meninges (Extended Data Fig. 9d) demonstrated a significant increase in the number of macrophages upon lymphatic ablation compared to both control groups (Extended Data Fig. 9e), which might be correlated with increased amyloid-β deposition and inflammation in the meninges PubMed:30046111

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Confidence
High
MeSH
Meninges

a(CHEBI:"GW 3965") decreases path(MESH:Inflammation) View Subject | View Object

Similarly, stimulation of microglia with the LXR agonist, GW3965, acts simultaneously to suppress inflammation and promote fibrillar Ab stimulated phagocytosis [47]. PubMed:21718217

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Confidence
Medium

a(MESH:Acetylcholine) decreases path(MESH:Inflammation) View Subject | View Object

Together with that re- leased by vagal nerve endings, ACh can also contribute to the cholinergic control of inflammation PubMed:28901280

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p(HGNC:CHRNA7) regulates path(MESH:Inflammation) View Subject | View Object

α7-containing receptors are expressed in neurons and non-excitable cells in order to mediate pro-proliferative, sur- vival and anti-inflammatory signalling. PubMed:28901280

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MeSH
GABAergic Neurons

act(p(HGNCGENEFAMILY:Caspases)) association path(MESH:Inflammation) View Subject | View Object

First, inflammation, which is a common feature of AD, may contribute to tau pathology by activating caspases. Treating cells with the prostaglandin cyclopentenone byproduct PGJ2 increased caspase activity and increased cleaved tau (62). PubMed:24027553

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Review

path(MESH:"Alzheimer Disease") positiveCorrelation path(MESH:Inflammation) View Subject | View Object

First, inflammation, which is a common feature of AD, may contribute to tau pathology by activating caspases. Treating cells with the prostaglandin cyclopentenone byproduct PGJ2 increased caspase activity and increased cleaved tau (62). PubMed:24027553

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Text Location
Review

p(HBP:"Tau isoform F (441 aa)", var("p.Ile277Pro"), var("p.Ile308Pro"), var("p.Lys280del")) causesNoChange path(MESH:Inflammation) View Subject | View Object

The antiaggregant TauRDΔKPP slices had ramified form of microglia with 6-7 branches on an average indicating that the microglial cells were in their normal physiologically active form and there is no sign of inflammation (Fig 3d, bars 1 and 2). PubMed:29202785

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p(HBP:"Tau isoform F (441 aa)", var("p.Lys280del")) increases path(MESH:Inflammation) View Subject | View Object

On the contrary, microglia in proaggregant TauRDΔK slices, were increased in number and were also observed with 2-3 branches on an average compared to age-matched controls and also the antiaggregant TauRDΔKPP slices (Fig. 3d, bar 3). This indicates that in the pro-aggregant TauRDΔK slices the microglia are in a reactive form, indicating that there is also enhanced inflammation PubMed:29202785

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bp(GO:"NIK/NF-kappaB signaling") association path(MESH:Inflammation) View Subject | View Object

Inflammation is one of major pathological changes in AD brains and NF-kB signalling plays an important role in inflammation and oxidative stress (Tong et al. 2005). PubMed:21329555

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path(MESH:"Alzheimer Disease") positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Inflammation is one of major pathological changes in AD brains and NF-kB signalling plays an important role in inflammation and oxidative stress (Tong et al. 2005). PubMed:21329555

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Annotations
MeSH
Brain

a(CHEBI:"gallic acid") decreases path(MESH:Inflammation) View Subject | View Object

It revealed potent anti-histone acetyltransferase (HAT) activity and inhibited RelA acetylation via direct inhibition of HAT enzymes and consequently down-regulation ofdiverse inflammatory signaling pathways [163]. PubMed:29179999

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a(CHEBI:"(+)-artemisinin") decreases path(MESH:Inflammation) View Subject | View Object

Moreover,it reveals promising anti-inflammatory actions through suppress-ing the activation of NF-B [238–240]. PubMed:29179999

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a(CHEBI:"vitamin D") decreases path(MESH:Inflammation) View Subject | View Object

The phosphorylation of the NF-B inflamma-tory pathway in A 25-35-stimulated microglial cells was inhibited by vitamin D2 via reducing ROS and inflammatory cytokines [207] PubMed:29179999

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Cell Ontology (CL)
microglial cell

a(CHEBI:berberine) decreases path(MESH:Inflammation) View Subject | View Object

Berberine suppressed inflammatory events occurring in several inflammation-related diseases [186,187]. PubMed:29179999

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a(CHEBI:oridonin) decreases path(MESH:Inflammation) View Subject | View Object

Besides, it attenuated cognitive disorders nd inflam-matory reactions in A 1-42-activated AD mice[194]. PubMed:29179999

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Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:155160) decreases path(MESH:Inflammation) View Subject | View Object

Beneficial effects of 4-O-methylhonokinol on memory were observed by the reduction of Aaggregation in A 1-42-injected mice and memory-impaired mice with its anti-oxidative and anti-inflammatory qualities [141–143]. PubMed:29179999

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MeSH
Alzheimer Disease

a(PUBCHEM:164676) decreases path(MESH:Inflammation) View Subject | View Object

Moreover, tanshinone IIA inhibited apoptosis in A 25-35-induced cells [232] and exerted anti-inflammatory activity in atherosclerosis and neuroprotective activity in cerebral ischemia/reperfusion impairment [233,234] PubMed:29179999

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MeSH
Atherosclerosis

a(PUBCHEM:444795) decreases path(MESH:Inflammation) View Subject | View Object

Retinoic acid showed anti-inflammatory qualities via suppressing the expression of the inflammatory mediators IL-6, IL-12 and TNF- [216–219] and mod-ulating NF-B signaling [220,221]. PubMed:29179999

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p(FPLX:NFkappaB) association path(MESH:Inflammation) View Subject | View Object

In the nervous system, NF-κB has been proposed to serve important function by acting as a transcription regulator: it has roles in inflammation, neuronal survival, differentiation, apoptosis, neurite outgrowth, and synaptic plasticity [5], which are impaired in the progression of various neurodegenerative diseases especially in AD. PubMed:27288790

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Annotations
MeSH
Nervous System

p(HGNC:NOS2) increases path(MESH:Inflammation) View Subject | View Object

Tetrandrine, is an herb-derived bisbenzylioquinoline alkaloid, may be a potent inhibitor of NF-κB activation and can inhibit the expression of iNOS and COX-2 which are involved in pro-inflammation. PubMed:27288790

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p(HGNC:PTGS2) increases path(MESH:Inflammation) View Subject | View Object

Tetrandrine, is an herb-derived bisbenzylioquinoline alkaloid, may be a potent inhibitor of NF-κB activation and can inhibit the expression of iNOS and COX-2 which are involved in pro-inflammation. PubMed:27288790

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path(MESH:"Alzheimer Disease") positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Inflammation is a key pathological hall mark of AD [61,62], NF-κB is considered as a primary regulator of inflammatory processes [10]. PubMed:27288790

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p(HGNC:ADNP) association path(MESH:Inflammation) View Subject | View Object

ADNP expression in lymphocytes correlates with inflammation levels (36), disease state, and autophagy (13), as well as intelligence (40). PubMed:30106381

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a(CHEBI:heme) increases path(MESH:Inflammation) View Subject | View Object

Extracellular hemoglobin and heme are pro-oxidative, proinflammatory, and cytotoxic [10–12], and can contribute to the pathology of hemolytic diseases. PubMed:26875449

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Text Location
Review

a(CHEBI:"carbon monoxide") decreases path(MESH:Inflammation) View Subject | View Object

Carbon monoxide has vasodilatory, anti-proliferative, anti-inflammatory and antioxidant properties, whereas bilirubin, the product of biliverdin reductase, is an antioxidant (Baranano et al, 2002). PubMed:25307023

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Annotations
Cell Ontology (CL)
macrophage
Text Location
Review

a(CHEBI:"iron(2+)") increases path(MESH:Inflammation) View Subject | View Object

These concepts challenged the idea that the cytotoxic and inflammatory effects of heme were exclusively mediated by the oxidative capability of the Fe associated with the amphipathic property of the porphyrin ring. PubMed:24904418

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Review

a(CHEBI:"iron(2+)") increases path(MESH:Inflammation) View Subject | View Object

Thus, the antioxidant, anticoagulant, anti-proliferative and vasodilating effects of the HMOX1 and biliverdin reductase systems probably compensate for the nitric oxide (NO) scavenging, vasoconstrictive, proliferative, inflammatory and pro-oxidant effects of circulating free haemoglobin, haem and haem-iron, which are discussed below (Rother et al, 2005). PubMed:25307023

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Cell Ontology (CL)
macrophage
Text Location
Review

a(CHEBI:"iron(2+)") positiveCorrelation path(MESH:Inflammation) View Subject | View Object

There are in vitro and animal model data linking increased free Hb, heme, and iron to inflammation, 6 infection,7 platelet (PLT) activation,8,9 vasculopathy, 10 and thrombosis. PubMed:29603246

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Text Location
Introduction

a(CHEBI:"nitric oxide") decreases path(MESH:Inflammation) View Subject | View Object

Both processes decrease the availability of NO, which normally maintains smooth muscle cell relaxation, inhibits platelet activation and aggregation, and has anti-inflammatory effects on the endothelium. PubMed:29929138

Appears in Networks:
Annotations
Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

a(CHEBI:heme) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

These results suggest that heme plays an essential role in kidney inflammation via regulating NLRP3-Caspase-1-IL-1b axis. PubMed:24464629

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Cell Ontology (CL)
macrophage
MeSH
Kidney
Text Location
Results

a(CHEBI:heme) increases path(MESH:Inflammation) View Subject | View Object

CO inhibits Hb oxidation and subsequently heme release, thus blocking heme accumulation in serum and preventing heme from exerting its inflammatory effects in the course of malaria disease (Ferreira et al., 2011). PubMed:24904418

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Annotations
Cell Ontology (CL)
erythrocyte
MeSH
Liver
MeSH
Malaria
Text Location
Review

a(CHEBI:heme) increases path(MESH:Inflammation) View Subject | View Object

During intravascular hemolysis the serum proteins responsible for removing heme get saturated and heme can exert its inflammatory effects. PubMed:24904418

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

a(CHEBI:heme) increases path(MESH:Inflammation) View Subject | View Object

Thus, the antioxidant, anticoagulant, anti-proliferative and vasodilating effects of the HMOX1 and biliverdin reductase systems probably compensate for the nitric oxide (NO) scavenging, vasoconstrictive, proliferative, inflammatory and pro-oxidant effects of circulating free haemoglobin, haem and haem-iron, which are discussed below (Rother et al, 2005). PubMed:25307023

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Cell Ontology (CL)
macrophage
Text Location
Review

a(CHEBI:heme) increases path(MESH:Inflammation) View Subject | View Object

Free plasma haemoglobin and haem also scavenge NO and have multiple pro-inflammatory and pro-oxidant properties that mediate many of the adverse effects of haemolysis. PubMed:25307023

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Annotations
Cell Ontology (CL)
macrophage
MeSH
Plasma
MeSH
Urine
Text Location
Review

a(CHEBI:heme) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

More recently, we have also shown that free heme is also released during storage and may mediate further inflammation28 PubMed:26202471

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Discussion

a(CHEBI:heme) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Free heme is a potent trigger of lipid peroxidation and a promoter of inflammation.4–6 PubMed:26794659

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Introduction

a(CHEBI:heme) increases path(MESH:Inflammation) View Subject | View Object

Increased plasma concentrations of cell-free heme, the breakdown product of 390 hemoglobin, promote activation and inflammation of endothelial cells and enhance 391 oxidative stress and vascular permeability (22). PubMed:28314763

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Annotations
Cell Ontology (CL)
endothelial cell
MeSH
Arteries
MeSH
Diabetes Mellitus
Text Location
Introduction

a(CHEBI:heme) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Free hemin is a cytotoxic molecule that mediates oxidative stress, endothelial activation, and inflammation, and it is implicated in malaria pathogenesis [40] and AKI, among others [41]. PubMed:28716864

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Annotations
Cell Ontology (CL)
neutrophil
MeSH
Serum
MeSH
Malaria
Text Location
Discussion

a(CHEBI:heme) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

There are in vitro and animal model data linking increased free Hb, heme, and iron to inflammation, 6 infection,7 platelet (PLT) activation,8,9 vasculopathy, 10 and thrombosis. PubMed:29603246

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Annotations
Text Location
Introduction

a(CHEBI:heme) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation and thrombosis. PubMed:29694434

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Text Location
Introduction

a(CHEBI:heme) increases path(MESH:Inflammation) View Subject | View Object

Administration of heme in healthy volunteers caused thrombophlebitis, demonstrating that it can cause vascular inflammation followed by vascular obstruction [18]. PubMed:29929138

Appears in Networks:
Annotations
Cell Ontology (CL)
erythrocyte
Cell Ontology (CL)
neutrophil
Cell Ontology (CL)
platelet
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

a(CHEBI:heme) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

In infectious diseases, such as malaria and sepsis, high amounts of cell-free hemoglobin and heme were found [8], suggesting that hemolysis during sepsis and systemic inflammation is of pathophysiological relevance. PubMed:29956069

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Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Liver
MeSH
Sepsis
Text Location
Review

a(CHEBI:heme) increases path(MESH:Inflammation) 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

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

a(CHEBI:malonaldehyde) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Malondialdehyde (MDA) represents evidence of systemic oxidative stress and inflammation [31], and is commonly used to estimate the level of lipid peroxidation. PubMed:30324533

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Annotations
MeSH
Hematoma
Text Location
Results

a(MESH:"Adenosine Diphosphate") positiveCorrelation path(MESH:Inflammation) View Subject | View Object

ADP released from haemolysed RBCs induces CD40LG release from platelets and lymphocytes, thereby contributing to the pro-inflammatory and pro-thrombotic environment (Helms et al, 2013). PubMed:25307023

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Annotations
Cell Ontology (CL)
endothelial cell
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

a(HM:"stored erythrocytes") positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Storage is known to result in increased hemolysis which in turn results in loss of NO-signaling, oxidative stress and inflammation post-transfusion. PubMed:26202471

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Discussion

a(MESH:"Erythrocytes, Abnormal") positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Under conditions of apoptosis or RBC damage, such as high shear rates, inflammation, or oxidative stress, RBCs can lose membrane asymmetry and expose phosphatidylserine [43]. PubMed:28458720

Appears in Networks:
Annotations
MeSH
Veins
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

a(MESH:"Reactive Oxygen Species") increases path(MESH:Inflammation) View Subject | View Object

These ROS then oxidize cell membrane constituents to induce cytotoxicity and promote inflammation and thrombosis. PubMed:25307023

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

a(MESH:"haptoglobin-hemoglobin complex") decreases path(MESH:Inflammation) View Subject | View Object

For example, Hp 2-2 has been associated with an increased susceptibility to diabetic cardiovascular disease; uptake of Hb-Hp(1-1) complexes by CD163 receptors is reportedly faster and its binding results in increased concentrations of anti-inflammatory mediators than Hb-Hp(2-2) complexes; and the angiogenic potency of Hp 2-2 is reportedly greater than that of Hp 1-1 [18]. PubMed:24486321

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Introduction

a(MESH:ferrylhemoglobin) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

We recently found that, contrary to other forms of oxidized hemoglobin, ferrylhemoglobin acts as a potent pro-inflammatory agonist in endothelial cells, leading to the up-regulation of adhesion molecules that support the recruitment of macrophages into the vessel wall.36 PubMed:20378845

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Cell Ontology (CL)
endothelial cell
MeSH
Atherosclerosis
Text Location
Discussion

a(MESH:ferrylhemoglobin) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

For example, HbFe41 (20 mM), but not HbFe31 or HbFe21, induced cytoskeletal reorganization, inflammation and disrupted barrier integrity in endothelial cells after 8 hours of incubation with the proteins. PubMed:26974230

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Cell Ontology (CL)
endothelial cell
MeSH
Mitochondria
Text Location
Discussion

bp(GO:"complement activation") increases path(MESH:Inflammation) View Subject | View Object

The circulating MPs can internalize free heme and transfer it to vascular endothelium, promoting vaso-occlusion, or amplify systemic inflammation via thrombin mediated activation of the complement system [57]. PubMed:28458720

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

bp(GO:"inflammatory response") positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Our data support the idea that heme-induced phenotypic switching of macrophages toward a proinflammatory phenotype can contribute to the exacerbation of inflammation and chronic tissue injury in hemolytic disorders and that Hx therapy could alleviate these pathophysiologic consequences by preventing macrophage inflammatory activation. PubMed:26675351

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Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Anemia, Sickle Cell
Text Location
Discussion

p(HGNC:HBB) increases path(MESH:Inflammation) View Subject | View Object

Thus, the antioxidant, anticoagulant, anti-proliferative and vasodilating effects of the HMOX1 and biliverdin reductase systems probably compensate for the nitric oxide (NO) scavenging, vasoconstrictive, proliferative, inflammatory and pro-oxidant effects of circulating free haemoglobin, haem and haem-iron, which are discussed below (Rother et al, 2005). PubMed:25307023

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

p(HGNC:HBB) increases path(MESH:Inflammation) View Subject | View Object

Free plasma haemoglobin and haem also scavenge NO and have multiple pro-inflammatory and pro-oxidant properties that mediate many of the adverse effects of haemolysis. PubMed:25307023

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

p(HGNC:HBB) increases path(MESH:Inflammation) View Subject | View Object

Depending on the scale, rate, and site of hemolysis, the primary adverse effects triggered by free Hb are vascular dysfunction, oxidative tissue damage, and altered inflammatory response [1], PubMed:26475040

Appears in Networks:
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MeSH
Anemia, Sickle Cell
Text Location
Abstract

p(HGNC:HBB) increases path(MESH:Inflammation) View Subject | View Object

Extracellular hemoglobin and heme are pro-oxidative, proinflammatory, and cytotoxic [10–12], and can contribute to the pathology of hemolytic diseases. PubMed:26875449

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Text Location
Review

p(HGNC:HBB) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Plasma hemoglobin scavenges nitric oxide and causes vasoconstriction, platelet aggregation and inflammation9,22–24. PubMed:27515135

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Introduction

p(HGNC:HBB) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

There are in vitro and animal model data linking increased free Hb, heme, and iron to inflammation, 6 infection,7 platelet (PLT) activation,8,9 vasculopathy, 10 and thrombosis. PubMed:29603246

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Text Location
Introduction

p(HGNC:HBB) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Our findings in the complex setting of critically ill pediatric cardiac surgery patients demonstrate that higher levels of free Hb and lower levels of haptoglobin are associated with serious postoperative clinical complications (infection, thrombosis, death), immunomodulation, and inflammation. PubMed:29603246

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Annotations
MeSH
Blood
MeSH
Anemia, Sickle Cell
Text Location
Discussion

p(HGNC:HBB) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation and thrombosis. PubMed:29694434

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Text Location
Introduction

p(HGNC:HBB) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

In infectious diseases, such as malaria and sepsis, high amounts of cell-free hemoglobin and heme were found [8], suggesting that hemolysis during sepsis and systemic inflammation is of pathophysiological relevance. PubMed:29956069

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Liver
MeSH
Sepsis
Text Location
Review

p(HGNC:HPX) decreases path(MESH:Inflammation) View Subject | View Object

In fact, hemolysis or heme injection in Hx−/− mice cause increased inflammation and severe renal damage compared to wild type (WT) mice (Tolosano et al., 1999; Vinchi et al., 2008). PubMed:24904418

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Cell Ontology (CL)
erythrocyte
Text Location
Review

p(MGI:Hpx) negativeCorrelation path(MESH:Inflammation) View Subject | View Object

In conclusion, an Hx-based therapy shows beneficial effects, in that it counteracts heme-induced proinflammatory activation of macrophages and attenuates some of its pathophysiologic consequences, such as chronic inflammation, hepatic fibrosis, and apoptosis (Figure 7E). PubMed:26675351

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Annotations
Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Anemia, Sickle Cell
Text Location
Results

complex(a(CHEBI:heme), p(MGI:Tlr4)) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

In that study, heme was shown to specifically bind to endothelial Toll-like receptors (TLR4) and trigger a cascade of inflammatory responses, which could be attributed to oxidation and degradation of cell-free Hb [73]. PubMed:24486321

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MeSH
Anemia, Sickle Cell
Text Location
Discussion

p(HGNC:SERPINA1) decreases path(MESH:Inflammation) View Subject | View Object

However A1AT has broader functions [26, 27], abrogating inflammation via both enzyme-inhibitory and noninhibitory mechanisms [47]. PubMed:28716864

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Annotations
Cell Ontology (CL)
neutrophil
MeSH
Serum
MeSH
Malaria
Text Location
Discussion

p(HGNC:HP) decreases path(MESH:Inflammation) View Subject | View Object

Probably the most important Hp-mediated abrogation of Hb toxicity is stabilization of heme within the central cavity of the Hb subunits, which almost completely prevents its dissociation and subsequent free heme-mediated oxidative reactions and inflammatory responses. PubMed:24486321

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Discussion

p(HGNC:CCL2) increases path(MESH:Inflammation) View Subject | View Object

Pro-inflammatory cytokines and chemokines [e.g., inter leukin 1B (IL1B), CXCL8 (also termed IL8), TNF and chemokine (C-C motif) ligand 2 (CCL2, also termed MCP1)], are upregulated in haemolytic disorders such as SCD (Qari et al, 2012). This pro-inflammatory cytokine milieu is crucial in mediating the pro-coagulant effects of vascular endothelial cells and promotes localized inflammation and thrombosis (Qari et al, 2012). PubMed:25307023

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

p(HGNC:CXCL8) increases path(MESH:Inflammation) View Subject | View Object

Pro-inflammatory cytokines and chemokines [e.g., inter leukin 1B (IL1B), CXCL8 (also termed IL8), TNF and chemokine (C-C motif) ligand 2 (CCL2, also termed MCP1)], are upregulated in haemolytic disorders such as SCD (Qari et al, 2012). This pro-inflammatory cytokine milieu is crucial in mediating the pro-coagulant effects of vascular endothelial cells and promotes localized inflammation and thrombosis (Qari et al, 2012). PubMed:25307023

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

p(HGNC:IL1B) increases path(MESH:Inflammation) View Subject | View Object

Although KC and IL-1β functions were not investigated during heme-induced inflammatory effects, TNF and LTB4 were described as essential inflammatory mediators during inflammatory events induced by heme. PubMed:24904418

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Annotations
Cell Ontology (CL)
erythrocyte
Text Location
Review

p(HGNC:IL1B) increases path(MESH:Inflammation) View Subject | View Object

Pro-inflammatory cytokines and chemokines [e.g., inter leukin 1B (IL1B), CXCL8 (also termed IL8), TNF and chemokine (C-C motif) ligand 2 (CCL2, also termed MCP1)], are upregulated in haemolytic disorders such as SCD (Qari et al, 2012). This pro-inflammatory cytokine milieu is crucial in mediating the pro-coagulant effects of vascular endothelial cells and promotes localized inflammation and thrombosis (Qari et al, 2012). PubMed:25307023

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Cell Ontology (CL)
endothelial cell
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

p(HGNC:TNF) increases path(MESH:Inflammation) View Subject | View Object

Although KC and IL-1β functions were not investigated during heme-induced inflammatory effects, TNF and LTB4 were described as essential inflammatory mediators during inflammatory events induced by heme. PubMed:24904418

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Cell Ontology (CL)
erythrocyte
Text Location
Review

p(HGNC:TNF) increases path(MESH:Inflammation) View Subject | View Object

Pro-inflammatory cytokines and chemokines [e.g., inter leukin 1B (IL1B), CXCL8 (also termed IL8), TNF and chemokine (C-C motif) ligand 2 (CCL2, also termed MCP1)], are upregulated in haemolytic disorders such as SCD (Qari et al, 2012). This pro-inflammatory cytokine milieu is crucial in mediating the pro-coagulant effects of vascular endothelial cells and promotes localized inflammation and thrombosis (Qari et al, 2012). PubMed:25307023

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Cell Ontology (CL)
endothelial cell
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

p(MGI:Casp1) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

These results suggest that heme induced activation of NLRP3-Caspase-1-IL-1b axis is involved in kidney inflammation in mice UUO model and that heme serves as a dangerous factor participates in this process. PubMed:24464629

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Cell Ontology (CL)
macrophage
MeSH
Kidney
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Results

p(MGI:Hmox1) decreases path(MESH:Inflammation) View Subject | View Object

The results showed that enforced HO-1 could efficiently decline the heme level in the lysates of ligated kidneys, and inhibit kidney inflammation characterized by down-regulation of NLRP3-Caspase- 1-IL-1b axis. PubMed:24464629

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Cell Ontology (CL)
macrophage
MeSH
Kidney
Text Location
Results

p(MGI:Hrg) decreases path(MESH:Inflammation) View Subject | View Object

Supplementary treatment of septic mice with purified HRG from human plasma remarkably suppressed immunothrombosis in the lungs as well as the associated inflammation. PubMed:29544683

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MeSH
Lung
MeSH
Sepsis
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Discussion

p(MGI:Il1b) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

These results suggest that heme induced activation of NLRP3-Caspase-1-IL-1b axis is involved in kidney inflammation in mice UUO model and that heme serves as a dangerous factor participates in this process. PubMed:24464629

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Cell Ontology (CL)
macrophage
MeSH
Kidney
Text Location
Results

p(MGI:Nlrp3) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

These results suggest that heme induced activation of NLRP3-Caspase-1-IL-1b axis is involved in kidney inflammation in mice UUO model and that heme serves as a dangerous factor participates in this process. PubMed:24464629

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Cell Ontology (CL)
macrophage
MeSH
Kidney
Text Location
Results

path(HP:"Acute kidney injury") positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Kidney inflammation is the major pathologic process of chronic kidney disease (CKD) and acute kidney injury (AKI) which cause significant morbidity and mortality in the general population [1]. PubMed:24464629

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Kidney
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Introduction

path(HP:"Chronic kidney disease") positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Kidney inflammation is the major pathologic process of chronic kidney disease (CKD) and acute kidney injury (AKI) which cause significant morbidity and mortality in the general population [1]. PubMed:24464629

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MeSH
Kidney
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Introduction

path(MESH:"Disseminated Intravascular Coagulation") association path(MESH:Inflammation) View Subject | View Object

Sepsis/systemic inflammation is frequently associated with disseminated intravascular coagulation (DIC) being a predictor of mortality in septic patients [84, 85]. PubMed:29956069

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Cell Ontology (CL)
erythrocyte
MeSH
Liver
MeSH
Sepsis
Text Location
Review

path(MESH:Hemolysis) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Furthermore, experiments of nature that lead to increased levels of chronic hemolysis, such as sickle cell anemia and paroxysmal nocturnal hemoglobinuria, provide evidence that low levels of hemolysis may be harmful, and contribute to inflammation, thrombosis, vasculopathy, and impaired host defenses against infection.1,11 PubMed:29603246

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MeSH
Anemia, Sickle Cell
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Introduction

path(MESH:Hemolysis) positiveCorrelation path(MESH:Inflammation) View Subject | View Object

Thus, hemolysis can act as a kind of amplifier of the complex response to an infection or injury [8, 15] and worsen the outcome from animals and patients with systemic inflammation, sepsis, or trauma [1–4, 10]. PubMed:29956069

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Out-Edges 41

path(MESH:Inflammation) negativeCorrelation act(a(MESH:"Lymphatic Vessels")) View Subject | View Object

Analysis of lymphoid and myeloid cell populations in the meninges (Extended Data Fig. 9d) demonstrated a significant increase in the number of macrophages upon lymphatic ablation compared to both control groups (Extended Data Fig. 9e), which might be correlated with increased amyloid-β deposition and inflammation in the meninges PubMed:30046111

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Confidence
High
MeSH
Meninges

path(MESH:Inflammation) increases path(MESH:"Renal Insufficiency") View Subject | View Object

During acute in- flammatory processes α7 AChRs attenuate renal failure induced by ische- mia/reperfusion by inhibiting pro-inflammatory cytokine expression, and subsequently decreasing cell apoptosis [180,201]. PubMed:22040696

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path(MESH:Inflammation) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

First, inflammation, which is a common feature of AD, may contribute to tau pathology by activating caspases. Treating cells with the prostaglandin cyclopentenone byproduct PGJ2 increased caspase activity and increased cleaved tau (62). PubMed:24027553

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path(MESH:Inflammation) association act(p(HGNCGENEFAMILY:Caspases)) View Subject | View Object

First, inflammation, which is a common feature of AD, may contribute to tau pathology by activating caspases. Treating cells with the prostaglandin cyclopentenone byproduct PGJ2 increased caspase activity and increased cleaved tau (62). PubMed:24027553

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path(MESH:Inflammation) increases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

Inflammation, a common feature of AD, can affect ligand affinity by making the pH more acidic, which promotes hyperphosphorylation of tau and induces conforma- tional changes in Aβ that hinder its clearance. PubMed:26195256

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MeSH
Hippocampus
MeSH
Temporal Lobe

path(MESH:Inflammation) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Inflammation is one of major pathological changes in AD brains and NF-kB signalling plays an important role in inflammation and oxidative stress (Tong et al. 2005). PubMed:21329555

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MeSH
Brain

path(MESH:Inflammation) association bp(GO:"NIK/NF-kappaB signaling") View Subject | View Object

Inflammation is one of major pathological changes in AD brains and NF-kB signalling plays an important role in inflammation and oxidative stress (Tong et al. 2005). PubMed:21329555

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path(MESH:Inflammation) association p(FPLX:NFkappaB) View Subject | View Object

In the nervous system, NF-κB has been proposed to serve important function by acting as a transcription regulator: it has roles in inflammation, neuronal survival, differentiation, apoptosis, neurite outgrowth, and synaptic plasticity [5], which are impaired in the progression of various neurodegenerative diseases especially in AD. PubMed:27288790

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MeSH
Nervous System

path(MESH:Inflammation) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Inflammation is a key pathological hall mark of AD [61,62], NF-κB is considered as a primary regulator of inflammatory processes [10]. PubMed:27288790

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path(MESH:Inflammation) association p(HGNC:ADNP) View Subject | View Object

ADNP expression in lymphocytes correlates with inflammation levels (36), disease state, and autophagy (13), as well as intelligence (40). PubMed:30106381

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path(MESH:Inflammation) positiveCorrelation p(HGNC:HBB) View Subject | View Object

Plasma hemoglobin scavenges nitric oxide and causes vasoconstriction, platelet aggregation and inflammation9,22–24. PubMed:27515135

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path(MESH:Inflammation) positiveCorrelation a(MESH:ferrylhemoglobin) View Subject | View Object

We recently found that, contrary to other forms of oxidized hemoglobin, ferrylhemoglobin acts as a potent pro-inflammatory agonist in endothelial cells, leading to the up-regulation of adhesion molecules that support the recruitment of macrophages into the vessel wall.36 PubMed:20378845

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Cell Ontology (CL)
endothelial cell
MeSH
Atherosclerosis
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Discussion

path(MESH:Inflammation) positiveCorrelation a(MESH:ferrylhemoglobin) View Subject | View Object

For example, HbFe41 (20 mM), but not HbFe31 or HbFe21, induced cytoskeletal reorganization, inflammation and disrupted barrier integrity in endothelial cells after 8 hours of incubation with the proteins. PubMed:26974230

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Cell Ontology (CL)
endothelial cell
MeSH
Mitochondria
Text Location
Discussion

path(MESH:Inflammation) positiveCorrelation path(HP:"Chronic kidney disease") View Subject | View Object

Kidney inflammation is the major pathologic process of chronic kidney disease (CKD) and acute kidney injury (AKI) which cause significant morbidity and mortality in the general population [1]. PubMed:24464629

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MeSH
Kidney
Text Location
Introduction

path(MESH:Inflammation) positiveCorrelation path(HP:"Acute kidney injury") View Subject | View Object

Kidney inflammation is the major pathologic process of chronic kidney disease (CKD) and acute kidney injury (AKI) which cause significant morbidity and mortality in the general population [1]. PubMed:24464629

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MeSH
Kidney
Text Location
Introduction

path(MESH:Inflammation) positiveCorrelation p(MGI:Nlrp3) View Subject | View Object

These results suggest that heme induced activation of NLRP3-Caspase-1-IL-1b axis is involved in kidney inflammation in mice UUO model and that heme serves as a dangerous factor participates in this process. PubMed:24464629

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Cell Ontology (CL)
macrophage
MeSH
Kidney
Text Location
Results

path(MESH:Inflammation) positiveCorrelation p(MGI:Casp1) View Subject | View Object

These results suggest that heme induced activation of NLRP3-Caspase-1-IL-1b axis is involved in kidney inflammation in mice UUO model and that heme serves as a dangerous factor participates in this process. PubMed:24464629

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Cell Ontology (CL)
macrophage
MeSH
Kidney
Text Location
Results

path(MESH:Inflammation) positiveCorrelation p(MGI:Il1b) View Subject | View Object

These results suggest that heme induced activation of NLRP3-Caspase-1-IL-1b axis is involved in kidney inflammation in mice UUO model and that heme serves as a dangerous factor participates in this process. PubMed:24464629

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Cell Ontology (CL)
macrophage
MeSH
Kidney
Text Location
Results

path(MESH:Inflammation) positiveCorrelation a(CHEBI:heme) View Subject | View Object

These results suggest that heme plays an essential role in kidney inflammation via regulating NLRP3-Caspase-1-IL-1b axis. PubMed:24464629

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Cell Ontology (CL)
macrophage
MeSH
Kidney
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Results

path(MESH:Inflammation) positiveCorrelation a(CHEBI:heme) View Subject | View Object

More recently, we have also shown that free heme is also released during storage and may mediate further inflammation28 PubMed:26202471

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path(MESH:Inflammation) positiveCorrelation a(CHEBI:heme) View Subject | View Object

Free heme is a potent trigger of lipid peroxidation and a promoter of inflammation.4–6 PubMed:26794659

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path(MESH:Inflammation) positiveCorrelation a(CHEBI:heme) View Subject | View Object

Free hemin is a cytotoxic molecule that mediates oxidative stress, endothelial activation, and inflammation, and it is implicated in malaria pathogenesis [40] and AKI, among others [41]. PubMed:28716864

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Cell Ontology (CL)
neutrophil
MeSH
Serum
MeSH
Malaria
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Discussion

path(MESH:Inflammation) positiveCorrelation a(CHEBI:heme) View Subject | View Object

There are in vitro and animal model data linking increased free Hb, heme, and iron to inflammation, 6 infection,7 platelet (PLT) activation,8,9 vasculopathy, 10 and thrombosis. PubMed:29603246

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Introduction

path(MESH:Inflammation) positiveCorrelation a(CHEBI:heme) View Subject | View Object

During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation and thrombosis. PubMed:29694434

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Introduction

path(MESH:Inflammation) positiveCorrelation a(CHEBI:heme) View Subject | View Object

In infectious diseases, such as malaria and sepsis, high amounts of cell-free hemoglobin and heme were found [8], suggesting that hemolysis during sepsis and systemic inflammation is of pathophysiological relevance. PubMed:29956069

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Cell Ontology (CL)
hepatocyte
MeSH
Liver
MeSH
Sepsis
Text Location
Review

path(MESH:Inflammation) positiveCorrelation complex(a(CHEBI:heme), p(MGI:Tlr4)) View Subject | View Object

In that study, heme was shown to specifically bind to endothelial Toll-like receptors (TLR4) and trigger a cascade of inflammatory responses, which could be attributed to oxidation and degradation of cell-free Hb [73]. PubMed:24486321

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MeSH
Anemia, Sickle Cell
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Discussion

path(MESH:Inflammation) positiveCorrelation a(MESH:"Adenosine Diphosphate") View Subject | View Object

ADP released from haemolysed RBCs induces CD40LG release from platelets and lymphocytes, thereby contributing to the pro-inflammatory and pro-thrombotic environment (Helms et al, 2013). PubMed:25307023

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Cell Ontology (CL)
endothelial cell
MeSH
Plasma
MeSH
Urine
MeSH
Anemia, Hemolytic, Autoimmune
Text Location
Review

path(MESH:Inflammation) positiveCorrelation a(HM:"stored erythrocytes") View Subject | View Object

Storage is known to result in increased hemolysis which in turn results in loss of NO-signaling, oxidative stress and inflammation post-transfusion. PubMed:26202471

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path(MESH:Inflammation) negativeCorrelation p(MGI:Hpx) View Subject | View Object

In conclusion, an Hx-based therapy shows beneficial effects, in that it counteracts heme-induced proinflammatory activation of macrophages and attenuates some of its pathophysiologic consequences, such as chronic inflammation, hepatic fibrosis, and apoptosis (Figure 7E). PubMed:26675351

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Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Anemia, Sickle Cell
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Results

path(MESH:Inflammation) positiveCorrelation bp(GO:"inflammatory response") View Subject | View Object

Our data support the idea that heme-induced phenotypic switching of macrophages toward a proinflammatory phenotype can contribute to the exacerbation of inflammation and chronic tissue injury in hemolytic disorders and that Hx therapy could alleviate these pathophysiologic consequences by preventing macrophage inflammatory activation. PubMed:26675351

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Cell Ontology (CL)
macrophage
MeSH
Liver
MeSH
Anemia, Sickle Cell
Text Location
Discussion

path(MESH:Inflammation) positiveCorrelation p(HGNC:HBB) View Subject | View Object

There are in vitro and animal model data linking increased free Hb, heme, and iron to inflammation, 6 infection,7 platelet (PLT) activation,8,9 vasculopathy, 10 and thrombosis. PubMed:29603246

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Introduction

path(MESH:Inflammation) positiveCorrelation p(HGNC:HBB) View Subject | View Object

Our findings in the complex setting of critically ill pediatric cardiac surgery patients demonstrate that higher levels of free Hb and lower levels of haptoglobin are associated with serious postoperative clinical complications (infection, thrombosis, death), immunomodulation, and inflammation. PubMed:29603246

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MeSH
Blood
MeSH
Anemia, Sickle Cell
Text Location
Discussion

path(MESH:Inflammation) positiveCorrelation p(HGNC:HBB) View Subject | View Object

During hemolysis, hemoglobin and heme released from red blood cells promote oxidative stress, inflammation and thrombosis. PubMed:29694434

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Text Location
Introduction

path(MESH:Inflammation) positiveCorrelation p(HGNC:HBB) View Subject | View Object

In infectious diseases, such as malaria and sepsis, high amounts of cell-free hemoglobin and heme were found [8], suggesting that hemolysis during sepsis and systemic inflammation is of pathophysiological relevance. PubMed:29956069

Appears in Networks:
Annotations
Cell Ontology (CL)
hepatocyte
MeSH
Liver
MeSH
Sepsis
Text Location
Review

path(MESH:Inflammation) positiveCorrelation a(MESH:"Erythrocytes, Abnormal") View Subject | View Object

Under conditions of apoptosis or RBC damage, such as high shear rates, inflammation, or oxidative stress, RBCs can lose membrane asymmetry and expose phosphatidylserine [43]. PubMed:28458720

Appears in Networks:
Annotations
MeSH
Veins
MeSH
Anemia, Sickle Cell
MeSH
beta-Thalassemia
Text Location
Review

path(MESH:Inflammation) positiveCorrelation a(CHEBI:"iron(2+)") View Subject | View Object

There are in vitro and animal model data linking increased free Hb, heme, and iron to inflammation, 6 infection,7 platelet (PLT) activation,8,9 vasculopathy, 10 and thrombosis. PubMed:29603246

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Text Location
Introduction

path(MESH:Inflammation) positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

Furthermore, experiments of nature that lead to increased levels of chronic hemolysis, such as sickle cell anemia and paroxysmal nocturnal hemoglobinuria, provide evidence that low levels of hemolysis may be harmful, and contribute to inflammation, thrombosis, vasculopathy, and impaired host defenses against infection.1,11 PubMed:29603246

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

path(MESH:Inflammation) positiveCorrelation path(MESH:Hemolysis) View Subject | View Object

Thus, hemolysis can act as a kind of amplifier of the complex response to an infection or injury [8, 15] and worsen the outcome from animals and patients with systemic inflammation, sepsis, or trauma [1–4, 10]. PubMed:29956069

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Review

path(MESH:Inflammation) increases a(MESH:"Cell-Derived Microparticles") View Subject | View Object

MPs are small membrane-derived vesicles that are shed upon activation, inflammation, or cell death/damage. PubMed:29929138

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Cell Ontology (CL)
platelet
MeSH
Endothelium
MeSH
Hemoglobinuria, Paroxysmal
Text Location
Discussion

path(MESH:Inflammation) association path(MESH:"Disseminated Intravascular Coagulation") View Subject | View Object

Sepsis/systemic inflammation is frequently associated with disseminated intravascular coagulation (DIC) being a predictor of mortality in septic patients [84, 85]. PubMed:29956069

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Cell Ontology (CL)
erythrocyte
MeSH
Liver
MeSH
Sepsis
Text Location
Review

path(MESH:Inflammation) positiveCorrelation a(CHEBI:malonaldehyde) View Subject | View Object

Malondialdehyde (MDA) represents evidence of systemic oxidative stress and inflammation [31], and is commonly used to estimate the level of lipid peroxidation. PubMed:30324533

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MeSH
Hematoma
Text Location
Results

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

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.