IL-33

IL-33

Interleukin-33 (IL-33, NF-HEV, DVS27) is a cytokine that belongs to the IL-1 family. It is expressed by endothelial cells, fibroblasts, bronchial and epithelial cells and some immune cells such as macrophages and dendritic cells. Full length IL-33 (30 kDa) is released upon cellular necrosis and is processed by caspase-3 and caspase-7 to the less active 20-22 kDa forms. IL-33 signaling is mediated by its receptor ST2 which exists in a soluble form (sST2) and as a transmembrane receptor (ST2L). Binding to ST2L causes activation of NF-kB and MAPK pathway. sST2 is thought to act as a decoy receptor attenuating the biological activity of IL-33. IL-33 mainly promotes Th2 cytokines like IL-4, IL-5 and IL-13 and it is able to activate cells of the innate and adaptive immune system. Elevated levels of IL-33 have been observed in chronic inflammatory diseases like asthma, rheumatoid arthritis, osteoarthritis, psoriatic arthritis, SLE, UC, Crohn’s disease. Recent studies have suggested that IL-33 may play a role in cardio vascular disorders; IL-33 expression has been seen in coronary artery smooth muscle cells, coronary artery endothelium, in non-HEV endothelial cells, and in cardiac fibroblasts. Early after acute myocardial infarction the levels of sST2, the IL-33 decoy, are elevated. Studies have also shown that IL-33/ST2 signaling may play an important protective role in CV disease. Therefore IL-33 may either promote the resolution of inflammation or drive disease pathology. Manipulation of the IL-33/sT2 pathway is being looked at as a promising method to treat or prevent various inflammatory disorders

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