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a(CHEBI:lipopolysaccharide) increases p(MGI:Il1b) View Subject | View Object

Our results showed that intraperitoneal injection of LPS (1 mg/kg) caused a significant elevation of plasma IL-1b (Mann–Whitney U=3, Z=-2.988, P=0.003), IL-6 (Mann–Whitney U=0, Z=-3.366, P=0.001) and TNFa (Mann– Whitney U=0, Z=-3.508, P<0.001) 4 h after the LPS challenge whereas in mice co-treated with an intraperitoneal injection of anatabine (2 mg/kg) and LPS, a significant reduction in plasma IL-1b (Mann–Whitney U=7, Z=-2.645, P=0.008) and TNFa (Mann–Whitney U=4, Z=-2.941, P=0.003) levels was observed (Fig. 6) PubMed:23178521

a(CHEBI:lipopolysaccharide) increases p(MGI:Il1b) View Subject | View Object

An elevation of IL-6 (Mann–Whitney U=0, Z=-3.487, P<0.001), IL1b (Mann– Whitney U=0, Z=-3.24, P=0.001) and TNFa (Mann–Whitney U=0, Z=-3.361, P=0.001) was observed in the spleen of LPS challenged mice (Fig. 7) PubMed:23178521

a(CHEBI:lipopolysaccharide) increases p(MGI:Il1b) View Subject | View Object

Similarly, IL-1b (Mann–Whitney U=0, Z=-3.098, P=0.002), IL-6 (Mann–Whitney U=0, Z=-3.363, P<0.001) and TNF-a levels (Mann–Whitney U=0, Z=-3.361, P=0.001) were elevated in the kidney following the LPS challenge (data not shown) PubMed:23178521

composite(a(CHEBI:Anatabine), a(CHEBI:lipopolysaccharide)) decreases p(MGI:Il1b) View Subject | View Object

Our results showed that intraperitoneal injection of LPS (1 mg/kg) caused a significant elevation of plasma IL-1b (Mann–Whitney U=3, Z=-2.988, P=0.003), IL-6 (Mann–Whitney U=0, Z=-3.366, P=0.001) and TNFa (Mann– Whitney U=0, Z=-3.508, P<0.001) 4 h after the LPS challenge whereas in mice co-treated with an intraperitoneal injection of anatabine (2 mg/kg) and LPS, a significant reduction in plasma IL-1b (Mann–Whitney U=7, Z=-2.645, P=0.008) and TNFa (Mann–Whitney U=4, Z=-2.941, P=0.003) levels was observed (Fig. 6) PubMed:23178521

composite(a(CHEBI:Anatabine), a(CHEBI:lipopolysaccharide)) decreases p(MGI:Il1b) View Subject | View Object

Anatabine significantly inhibited LPS induced IL-6 (Mann–Whitney U=4, Z=-3.303, P=0.001), TNF-a (Mann–Whitney U=0, Z=-3.361, P=0.001) and IL-1b levels in the spleen (Mann–Whitney U=9, Z=-1.981, P=0.048) (Fig. 7) PubMed:23178521

a(CHEBI:Anatabine) decreases p(MGI:Il1b) View Subject | View Object

However, anatabine significantly suppressed the production of IL-1b, IL-6 and IL-17A in the serum of EAE mice (Fig. 2B) but did not significantly impact IFN-gamma and TNF-alpha PubMed:23383175

a(CHEBI:Anatabine) decreases p(MGI:Il1b) View Subject | View Object

Anatabine appears to fully suppress IL-1b, INF-gamma and TNF-a elevation in the spleen of EAE mice (Fig. 2C). PubMed:23383175

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

We found that IL-1b, IFN-gamma, TNF-alpha, IL-6 and IL-17A were significantly elevated in the serum of EAE mice compared to control non-immunized mice PubMed:23383175

path(MESH:Encephalomyelitis) increases p(MGI:Il1b) View Subject | View Object

A significant elevation of IL-1b, INF-gamma and TNF-alpha was observed in the spleen of EAE mice compared to control non immunized animals PubMed:23383175

a(GO:"neurofibrillary tangle") increases act(p(MGI:Il1b)) View Subject | View Object

Consistent with NFTs from human AD, mouse NFTs also caused significant activation scores for IFNG, TNF, IL-1B, as well as enrichment in other senescence associated JAK, STAT, CDKN2A and BCL2 predicted upstream regulators (Figure 1c) indicating translational relevance for using tauNFT mice to explore our hypothesis PubMed:30126037

p(MGI:Mapt, var("p.Pro301Leu")) increases p(MGI:Il1b) View Subject | View Object

Consistent with the transcriptomic profile in human NFT-bearing neurons and mouse brain tissue (Figure 1a-c), SASP genes were found to be upregulated in tauNFT brains, i.e., Il1b was 4- and 2-fold higher than CTL and tauWT, respectively; and Cxcl1 was 4-fold higher than both control genotypes; Tnfa was 13- and 8-fold higher than CTL and tauWT, respectively; Tlr4 was 3-fold higher than both control genotypes (Figure 2a-d) PubMed:30126037

p(MGI:Mefv) decreases sec(p(MGI:Il1b)) View Subject | View Object

One study found that Mefv deletion in mice lead to increased IL-1β release without influencing caspase 1 activity or inflammasome assembly. PubMed:23702978

p(MGI:Nlrp3) increases p(MGI:Il1b) View Subject | View Object

A recent report shows that IL-18 and IL-1β are secreted from primed murine dendritic cells in response to Listeria protein p60, but inhibiting NLRP3 reduces the production of IL-1β, but not IL-18 secretion (Schmidt and Lenz, 2012) PubMed:24561250

a(CHEBI:heme) increases p(MGI:Il1b) View Subject | View Object

ELISA analysis displayed that the concentration of IL-1b in culture supernatants was significantly enhanced after stimulated by heme and PPIX. PubMed:24464629

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a(CHEBI:heme) increases p(MGI:Il1b) View Subject | View Object

The effect of heme on IL-1b production initiated as early as 4 h after stimulation and displayed strict time- and dose-dependent manner (Fig. 1a– d). PubMed:24464629

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a(CHEBI:heme) increases p(MGI:Il1b) View Subject | View Object

These results demonstrate that heme could efficiently induce maturation and secretion of IL-1b in macrophages and primarily suggested that heme participates in immune response. PubMed:24464629

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a(CHEBI:protoporphyrin) increases p(MGI:Il1b) View Subject | View Object

ELISA analysis displayed that the concentration of IL-1b in culture supernatants was significantly enhanced after stimulated by heme and PPIX. PubMed:24464629

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act(p(MGI:Casp1)) increases p(MGI:Il1b) View Subject | View Object

These results suggest that heme induces maturation and secretion of IL-1b in macrophages through activating caspase-1 (Fig. 2a). PubMed:24464629

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p(MGI:Hmox1) negativeCorrelation p(MGI:Il1b) 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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act(p(MGI:Nlrp3)) positiveCorrelation p(MGI:Il1b) View Subject | View Object

As expected, NLRP3+/+ macrophages were efficiently stimulated to secrete IL-1b by heme, and displayed dose-dependent (up to 40 lM) manner. PubMed:24464629

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act(p(MGI:Nlrp3)) positiveCorrelation p(MGI:Il1b) View Subject | View Object

These results demonstrate that free heme induces IL-1b through activating NLRP3 inflammasome via ASC and suggest that free heme plays an essential role in inflammation response as a dangerous signal. PubMed:24464629

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p(MGI:P2rx4) positiveCorrelation p(MGI:Il1b) View Subject | View Object

Therefore, knockdown of P2X4R and double knockdown of P2X7R plus P2X4R were performed by shRNA in macrophages and the result showed that P2X4R knockdown also partially inhibit the heme induced IL-1b secretion and double knockdown of P2X7R plus P2X4R almost completely depressed the IL-1b secretion (Fig. 3d). PubMed:24464629

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p(MGI:P2rx7) positiveCorrelation p(MGI:Il1b) View Subject | View Object

Western blotting showed that deficiency of P2X7R partially inhibited the secretion of mature IL-1b that heme induced (Fig. 3c). PubMed:24464629

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act(p(MGI:Pycard)) positiveCorrelation p(MGI:Il1b) View Subject | View Object

Knockdown of ASC significantly inhibits the secretion of IL-1b, which primarily suggests that Inflammation/ASC axis is involved in the heme-mediated maturation and secretion of IL-1b (Fig. 2b). PubMed:24464629

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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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Out-Edges 8

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

We found that IL-1b, IFN-gamma, TNF-alpha, IL-6 and IL-17A were significantly elevated in the serum of EAE mice compared to control non-immunized mice PubMed:23383175

p(MGI:Il1b) positiveCorrelation act(p(MGI:Pycard)) View Subject | View Object

Knockdown of ASC significantly inhibits the secretion of IL-1b, which primarily suggests that Inflammation/ASC axis is involved in the heme-mediated maturation and secretion of IL-1b (Fig. 2b). PubMed:24464629

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macrophage
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p(MGI:Il1b) positiveCorrelation act(p(MGI:Nlrp3)) View Subject | View Object

As expected, NLRP3+/+ macrophages were efficiently stimulated to secrete IL-1b by heme, and displayed dose-dependent (up to 40 lM) manner. PubMed:24464629

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Cell Ontology (CL)
macrophage
MeSH
Kidney
Text Location
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p(MGI:Il1b) positiveCorrelation act(p(MGI:Nlrp3)) View Subject | View Object

These results demonstrate that free heme induces IL-1b through activating NLRP3 inflammasome via ASC and suggest that free heme plays an essential role in inflammation response as a dangerous signal. PubMed:24464629

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Cell Ontology (CL)
macrophage
MeSH
Kidney
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p(MGI:Il1b) positiveCorrelation p(MGI:P2rx7) View Subject | View Object

Western blotting showed that deficiency of P2X7R partially inhibited the secretion of mature IL-1b that heme induced (Fig. 3c). PubMed:24464629

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macrophage
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Kidney
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p(MGI:Il1b) positiveCorrelation p(MGI:P2rx4) View Subject | View Object

Therefore, knockdown of P2X4R and double knockdown of P2X7R plus P2X4R were performed by shRNA in macrophages and the result showed that P2X4R knockdown also partially inhibit the heme induced IL-1b secretion and double knockdown of P2X7R plus P2X4R almost completely depressed the IL-1b secretion (Fig. 3d). PubMed:24464629

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macrophage
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Kidney
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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
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Kidney
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p(MGI:Il1b) negativeCorrelation p(MGI:Hmox1) 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

Appears in Networks:
Annotations
Cell Ontology (CL)
macrophage
MeSH
Kidney
Text Location
Results

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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.