Description
IL-33 is a 30 kD proinflammatory cytokine that belongs to the IL-1 superfamily. It signals inflammation in the body via the stimulation of macrophages, neutrophils, B cells, Th2 cells, eosinophils, basophils and mast cells. IL-33 is a ligand for IL33R (ST2), which is part of a cytokine receptor gene cluster that includes IL-1RI and IL-1RII. IL-33 binds ST2 and complexes with the IL-1R Accessory Protein (IL-1R-AcP) to form a functional signaling receptor complex facilitating the activation of NF-B and MAP kinase signaling pathways resulting in the production of type 2 cytokines from polarized Th2 cells. IL-33R can exist as a type I transmembrane glycoprotein or a soluble glycoprotein. The soluble IL-33R is thought to serve as a decoy receptor which competitively antagonizes the binding of IL-33 thereby reducing its biological effects. IL-33 has been linked with asthma, allergies, endometriosis, and hay fever. In addition, IL-33 resides in keratinocytes of the skin and is thought to trigger the itching associated with dermatitis when subjected to irritation or allergic conditions. Furthermore, in APP/PS1 mice, IL-33 has been shown to be effective in reversing the buildup and preventing the new formation of amyloid plaques that are characteristic of Alzheimer’s disease. However, the action of extracellular IL-33 is limited due to rapid oxidation that causes a molecular conformational change which prevents it from binding to the ST2 receptor