title: IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines.
abstract: Cytokines of the interleukin-1 (IL-1) family, such as IL-1 alpha/beta and IL-18, have important functions in host defense, immune regulation, and inflammation. Insight into their biological functions has led to novel therapeutic approaches to treat human inflammatory diseases. Within the IL-1 family, IL-1 alpha/beta, IL-1Ra, and IL-18 have been matched to their respective receptor complexes and have been shown to have distinct biological functions. The most prominent orphan IL-1 receptor is ST 2. This receptor has been described as a negative regulator of Toll-like receptor-IL-1 receptor signaling, but it also functions as an important effector molecule of T helper type 2 responses. We report a member of the IL-1 family, IL-33, which mediates its biological effects via IL-1 receptor ST 2, activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated cytokines from in vitro polarized T(H)2 cells. In vivo, IL-33 induces the expression of IL-4, IL-5, and IL-13 and leads to severe pathological changes in mucosal organs.
authors.affiliation: Schering-Plough Biopharma (formerly DNAX Research, Inc.), 901 California Avenue, Palo Alto, California 94304, USA.
authors.forename: Jochen
authors.initials: J
authors.lastname: Schmitz
authors.forename: Alexander
authors.initials: A
authors.lastname: Owyang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Oldham
authors.forename: Yaoli
authors.initials: Y
authors.lastname: Song
authors.forename: Erin
authors.initials: E
authors.lastname: Murphy
authors.forename: Terril K
authors.initials: TK
authors.lastname: McClanahan
authors.forename: Gerard
authors.initials: G
authors.lastname: Zurawski
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Moshrefi
authors.forename: Jinzhong
authors.initials: J
authors.lastname: Qin
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Gorman
authors.forename: J Fernando
authors.initials: JF
authors.lastname: Bazan
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kastelein
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D016764:Cell Polarity; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004789:Enzyme Activation; D004804:Eosinophils / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000276:immunology*; D008407:Mast Cells / Q000378:metabolism; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D010802:Phylogeny; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1 / Q000276:immunology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D016207:Cytokines; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; C486189:Il1rl1 protein, mouse; C506535:Il33 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D007378:Interleukins; D008565:Membrane Proteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D017472:Receptors, Interleukin-1; D020928:Mitogen-Activated Protein Kinases