Interleukin-33 (IL-33) is a recently identified member of the IL-1 family of cytokines whose other members include IL-1???, IL-1Ra and IL-18 (1,2). Its receptor has been shown to be ST2, an IL-1 receptor family member that also acts as a negative regulator of TLR-IL-1R signaling (1,3) and IL-1R accessory protein (IL-1RAcP) (4). Receptor binding of IL-33 activates NF-?B and MAP kinases and induces the expression of TH2-associated cytokines such as IL-4, IL-5 and IL-6. Prolonged IL-33 treatment of mice led to the development of eosinophilia, splenomegaly, and severe pathological changes in mucosal organs such as lungs, esophagus and small intestine (2). Recent experiments have shown that IL-33 can also co-localize with heterochromatin and possesses transcriptional repressor activities, indicating that IL-33 may function as both a proinflammatory cytokine and an intracellular nuclear factor with transcriptional regulatory properties (5).
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