IL1 and megakaryocytes in obesity (WP2865)

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. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2865 CPTAC Assay Portal]
last edited

Authors

Khanspers, MaintBot, MirellaKalafati, Jmelius, AMTan, and Susan

Cited In

Organism

Homo sapiens

Communities

Diseases

Annotations

Disease Ontology: overnutrition obesity

Pathway Ontology: obesity pathway interleukin-1 signaling pathway

Participants

Label Type Compact Identifier
p38/MAPK pathway Pathway wikipathways:WP400
IL1R1 GeneProduct ncbigene:3554
PAR1 GeneProduct ncbigene:2149
ICAM1 GeneProduct ncbigene:3383
IL1B GeneProduct ncbigene:3553
TIMP2 GeneProduct ncbigene:7077
SELENBP1 GeneProduct ncbigene:8991
MMP9 GeneProduct ncbigene:4318
PLA2G7 GeneProduct ncbigene:7941
IRAK1 GeneProduct ncbigene:3654
TLR1 GeneProduct ncbigene:7096
IL18 GeneProduct ncbigene:3606
MYD88 GeneProduct ncbigene:4615
TIMP1 GeneProduct ncbigene:7076
CCR3 GeneProduct ncbigene:1232
PIK3CA GeneProduct ncbigene:5290
NLRP3 GeneProduct ncbigene:114548
FCER1A GeneProduct ncbigene:2205
MYD88 GeneProduct ncbigene:4615
Thrombin GeneProduct ncbigene:2147
IFNG GeneProduct ncbigene:3458
S100A9 GeneProduct ncbigene:6280
HBEGF GeneProduct ncbigene:1839
CCL2 GeneProduct ncbigene:6347
TLR2 GeneProduct ncbigene:7097
ERKpathway Pathway None
MMP9 GeneProduct ncbigene:4318
IL1R1 GeneProduct ncbigene:3554
NFKB1 GeneProduct ncbigene:4790
IL1B GeneProduct ncbigene:3553
IL1R1 GeneProduct ncbigene:3554

References

  1. Beaulieu LM, Lin E, Mick E, Koupenova M, Weinberg EO, Kramer CD, et al. 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 Mar;34(3):552–64. PubMed Europe PMC Scholia