Interleukin-33 (IL-33; HF-NEV; IL-1F11), a member of the IL-1 family of cytokines, is expressed by many cell types following pro-inflammatory stimulation and is thought to be released on cell lysis. The 30kD human IL33 is converted by CASP1 to a 18kD protein. IL33 binds to and signals through ST2 (IL1R1) and its stimulation recruits MYD88, IRAK, IRAK4, and TRAF6, followed by phosphorylation of ERK1 (MAPK3)/ERK2 (MAPK1), p38 (MAPK14), and JNK. The ability of IL-33 to target numerous immune cell types, like Th2-like cells, mast cells, and B1 cells, and to induce cytokine and chemokine production underlines its potential in influencing the outcome of a wide range of diseases, such as arthritis, asthma, atopic allergy & anaphylaxis, cardiovascular disease/atherosclerosis, nervous system diseases, and sepsis.
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