IL1 and megakaryocytes in obesity (Homo sapiens)

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1Increased adhesionIncreased ploidyTranscripts increased in mouse data(Human homologs)Platelets with increased inflammatoryand thrombotic transcriptsHigh Fat DietTranscripts increased inFramingham Heart Studyp38/MAPK pathwayIL1R1PAR1ICAM1IL1BTIMP2SELENBP1MMP9PLA2G7IRAK1TLR1IL18MYD88TIMP1CCR3PIK3CANLRP3FCER1AMYD88ThrombinIFNGS100A9HBEGFCCL2TLR2ERKpathwayMMP9Active integrinsPlateletWhite Blood CellAdhesionAggregationHeterotypic AggregateFormationMegakaryocyteIL1R1NFKB1IL1BIL1R1


Description

Schematic of the effects of interleukin (IL)1-beta/IL1R1 on megakaryocyte and platelet function. A high fat diet will cause megakaryocytes to produce platelets with an increase in both inflammatory and thrombotic genes.

IL1-beta in circulation as a result of increased body weight will bind IL1R1 on megakaryocytes. This interaction leads to the activation of the nuclear factor (NF)kB, PI3K/Akt, and mitogen activated protein kinase (MAPK) (ERK and p38) pathways. As a result, there is an increase in megakarycoyte maturation, including increased adhesion, increases in ploidy, and increases in mRNA production of inflammatory and thrombotic genes. IL1-beta can also bind IL1R1 on platelets and either enhance aggregation induced by agonists or promote adhesion and heterotypic aggregate formation.

Some of the data used to create the pathway was generated in mouse (noted in pathway), however the pathway represents human homologs of those genes.

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Bibliography

  1. Beaulieu LM, Lin E, Mick E, Koupenova M, Weinberg EO, Kramer CD, Genco CA, Tanriverdi K, Larson MG, Benjamin EJ, Freedman JE; ''Interleukin 1 receptor 1 and interleukin 1β regulate megakaryocyte maturation, platelet activation, and transcript profile during inflammation in mice and humans.''; Arterioscler Thromb Vasc Biol, 2014 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
123108view14:57, 3 July 2022EgonwMade a pathway clickable
120807view11:03, 11 January 2022SusanOntology Term : 'interleukin-1 signaling pathway' added !
106600view19:38, 10 September 2019KhanspersModified description
105623view05:00, 10 August 2019KhanspersModified description
97642view14:34, 31 May 2018AMTanOntology Term : 'obesity' added !
88662view15:21, 12 August 2016JmeliusOntology Term : 'obesity disease pathway' added !
86165view13:42, 3 July 2016MirellaKalafatiModified title
81650view18:48, 21 August 2015Khanspersfixed unconnected interactions
78483view10:28, 7 January 2015MaintBotadded missing graphIds
78080view00:07, 1 December 2014Khanspersfixed unconnected interactions
77990view18:31, 4 November 2014KhanspersModified description
77989view18:22, 4 November 2014KhanspersOntology Term : 'overnutrition' added !
77988view18:21, 4 November 2014KhanspersModified description
77987view18:19, 4 November 2014Khanspersminor edits
77855view20:52, 22 October 2014Khansperschanged layout and added info on transcript data
77779view18:31, 17 October 2014KhanspersModified description
77778view18:29, 17 October 2014KhanspersAdded lit ref
77777view18:27, 17 October 2014KhanspersNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
CCL2GeneProduct6347 (Entrez Gene)
CCR3GeneProduct1232 (Entrez Gene)
ERK pathwayPathway
FCER1AGeneProduct2205 (Entrez Gene)
HBEGFGeneProduct1839 (Entrez Gene)
ICAM1GeneProduct3383 (Entrez Gene)
IFNGGeneProduct3458 (Entrez Gene)
IL18GeneProduct3606 (Entrez Gene)
IL1BGeneProduct3553 (Entrez Gene)
IL1R1GeneProduct3554 (Entrez Gene)
IRAK1GeneProduct3654 (Entrez Gene)
MMP9GeneProduct4318 (Entrez Gene)
MYD88GeneProduct4615 (Entrez Gene)
NFKB1GeneProduct4790 (Entrez Gene)
NLRP3GeneProduct114548 (Entrez Gene)
PAR1GeneProduct2149 (Entrez Gene)
PIK3CAGeneProduct5290 (Entrez Gene)
PLA2G7GeneProduct7941 (Entrez Gene)
S100A9GeneProduct6280 (Entrez Gene)
SELENBP1GeneProduct8991 (Entrez Gene)
TIMP1GeneProduct7076 (Entrez Gene)
TIMP2GeneProduct7077 (Entrez Gene)
TLR1GeneProduct7096 (Entrez Gene)
TLR2GeneProduct7097 (Entrez Gene)
ThrombinGeneProduct2147 (Entrez Gene)
p38/MAPK pathwayPathwayWP400 (WikiPathways)

Annotated Interactions

No annotated interactions

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