IL-33 Protein, Canine

IL-33 Protein is a cytokine that binds to and activates the IL1RL1/ST2 receptor, leading to the activation of NF-kappa-B and MAPK signaling pathways in target cells. It plays a role in the maturation of Th2 cells and induces the secretion of T-helper type 2-associated cytokines. IL-33 is also involved in the activation of mast cells, basophils, eosinophils, and natural killer cells. It acts as a chemoattractant for Th2 cells and may function as an 'alarmin', amplifying immune responses during tissue injury. Additionally, IL-33 induces rapid mitochondrial rewiring via UCP2, reducing the generation of reactive oxygen species and preserving the integrity of the Krebs cycle, which is essential for the production of itaconate and subsequent differentiation of inflammation-resolving alternatively activated macrophages. In quiescent endothelial cells, IL-33 is constitutively and abundantly expressed in its uncleaved form, acting as a chromatin-associated nuclear factor with transcriptional repressor properties and sequestering nuclear NF-kappaB/RELA, resulting in lower expression of its target genes. However, this form is rapidly lost upon angiogenic or pro-inflammatory activation.