IL-33 Protein, Human (His)

IL-33 protein, functioning as a cytokine, binds to and signals through the IL1RL1/ST2 receptor, thereby activating the NF-kappa-B and MAPK signaling pathways in target cells. Its involvement in the maturation of Th2 cells contributes to the secretion of T-helper type 2-associated cytokines. Additionally, IL-33 plays a crucial role in the activation of mast cells, basophils, eosinophils, and natural killer cells. Acting as an enhancer of the polarization of alternatively activated macrophages, it serves as a chemoattractant for Th2 cells and may function as an 'alarmin,' amplifying immune responses during tissue injury. IL-33 induces rapid UCP2-dependent mitochondrial rewiring, mitigating the generation of reactive oxygen species and preserving the integrity of the Krebs cycle, which is essential for the persistent production of itaconate and subsequent GATA3-dependent differentiation of inflammation-resolving alternatively activated macrophages. In quiescent endothelia, the uncleaved form of IL-33 is constitutively and abundantly expressed, acting as a chromatin-associated nuclear factor with transcriptional repressor properties, potentially sequestering nuclear NF-kappaB/RELA and thereby lowering the expression of its targets; this form is rapidly lost upon angiogenic or pro-inflammatory activation.