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.This pathway was inferred from Homo sapiens pathway [http://wikipathways.org/instance/WP2865_r78483 WP2865(78483)] with a 96.0% conversion rate.b30HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3554HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2149HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3383HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3553HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7077HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8991HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4318HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7941HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3654HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3606HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4615HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7076HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1232HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5290HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:114548HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2205HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4615HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2147HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3458HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6280HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1839HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6347HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7097HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4318HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3554HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4790HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3553HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3554From mouse dataFrom Framingham Heart StudyovernutritionDOID:654Human Disease Ontologyobesity disease pathwayPW:0000540Pathway Ontology24458711PubMedInterleukin 1 receptor 1 and interleukin 1β regulate megakaryocyte maturation, platelet activation, and transcript profile during inflammation in mice and humans.Arterioscler Thromb Vasc Biol2014Beaulieu LMLin EMick EKoupenova MWeinberg EOKramer CDGenco CATanriverdi KLarson MGBenjamin EJFreedman JE