Il-33 (IL33) Antibody – Mouse Monoclonal

IL33 (MIM 608678) is a member of the IL1 (see MIM 147760) family that potently drives production of T helper-2 (Th2)-associated cytokines (e.g., IL4; MIM 147780). IL33 is a ligand for IL33R (IL1RL1; MIM 601203), an IL1 family receptor that is selectively expressed on Th2 cells and mast cells (summary by Yagami et al., 2010 [PubMed 20926795]).[supplied by OMIM, Jan 2011]

Function: Cytokine that binds to and signals through IL1RL1/ST2 and its stimulation recruits MYD88, IRAK1, IRAK4, and TRAF6, followed by phosphorylation of MAPK3/ERK1 and/or MAPK1/ERK2, MAPK14, and MAPK8. Induces T-helper type 2-associated cytokines. Acts as a chemoattractant tor Th2 cells, and may function as an "alarmin", that amplifies immune responses during tissue injury. Ref.3 Ref.10 Ref.11 Ref.12 Ref.13 Ref.17 Ref.18In quiescent endothelia the uncleaved form is constitutively and abundantly expressed, and acts as a chromatin-associated nuclear factor with transcriptional repressor properties, it may sequester nuclear NF-kappaB/RELA, lowering expression of its targets. This form is rapidely lost upon angiogenic or proinflammatory activation. Ref.3 Ref.10 Ref.11 Ref.12 Ref.13 Ref.17 Ref.18

Subunit structure: Forms a 1:1:1 heterotrimeric complex with its primary high-affinity receptor IL1RL1 and the coreceptor IL1RAP. Ref.20

Subcellular location: Nucleus. Chromosome. Cytoplasmic vesicle › secretory vesicle. Secreted. Note: Associates with heterochromatin and mitotic chromosomes. Translocation from the nucleus occurs upon biomechanical strain, depends on an intact microtubule network, and is ATP-dependent. Ref.1 Ref.3 Ref.11 Ref.12 Ref.13 Ref.17 Ref.18

Tissue specificity: Expressed at high level in high endothelial venules found in tonsils, Peyer patches and mesenteric lymph nodes. Almost undetectable in placenta.

Domain: The homeodomain-like HTH domain mediates nuclear localization and heterochromatin association. Ref.11

Post-translational modification: Proteolytically converted to a mature form by CASP1 in vitro and calpains in vivo. Caspase-mediated proteolysis, once thought to activate IL33, rather acts as a switch to dampen its activity. Cathepsin G and elastase can cleave IL33 and generate highly active forms in activated neutrophils (IL-33(95-270), IL-33(99-270) and IL-33(109-270)). Proteolysis is not strictly required for biological activity.

Sequence similarities: Belongs to the IL-1 family. Highly divergent.