Interleukin 33
Interleukin 33 (IL33) is a protein that in humans is encoded by the IL33 gene.[2]
Interleukin 33 is a member of the IL-1 family that potently drives production of T helper-2 (Th2)-associated cytokines (e.g., IL-4). IL33 is a ligand for IL33R (IL1RL1), an IL-1 family receptor that is highly expressed on Th2 cells, mast cells and group 2 innate lymphocytes.[3]
IL-33 is expressed on a wide variety of cell types, including fibroblasts, mast cells, dendritic cells, macrophages, osteoblasts, endothelial cells, and epithelial cells.[4]
IL-33 is effective in reversing Alzheimer-like symptoms in APP/PS1 mice, by reversing the buildup and preventing the new formation of amyloid plaques.[5]
Function
Interleukin 33 (IL-33) is a cytokine belonging to the IL-1 superfamily. IL-33 induces helper T cells, mast cells, eosinophils and basophils to produce type 2 cytokines. This cytokine was previously named NF-HEV 'nuclear factor (NF) in high endothelial venules' (HEVs) since it was originally identified in these specialized cells.[6] IL-33 mediates its biological effects by interacting with the receptors ST2 (also known as IL1RL1) and IL-1 Receptor Accessory Protein (IL1RAP), activating intracellular molecules in the NF-κB and MAP kinase signaling pathways that drive production of type 2 cytokines (e.g. IL-5 and IL-13) from polarized Th2 cells. The induction of type 2 cytokines by IL-33 in vivo is believed to induce the severe pathological changes observed in mucosal organs following administration of IL-33.[7][8]
Structure
IL-33 is a member of the IL-1 superfamily of cytokines, a determination based in part on the molecules β-trefoil structure, a conserved structure type described in other IL-1 cytokines, including IL-1α, IL-1β, IL-1Ra and IL-18. In this structure, the 12 β-strands of the β-trefoil are arranged in three pseudorepeats of four β-strand units, of which the first and last β-strands are antiparallel staves in a six-stranded β-barrel, while the second and third β-strands of each repeat form a β-hairpin sitting atop the β-barrel. IL-33 is a ligand that binds to a high-affinity receptor family member ST2. The complex of these two molecules with IL-1RAcP indicates a ternary complex formation. The binding area appears to be a mix of polar and non-polar regions that create a specific binding between ligand and receptor. The interface between the molecules has been shown to be extensive. Structural data on the IL-33 molecule was determined by solution NMR and small angle X-ray scattering.[9]
References
- ↑ PDB: 2KLL; Lingel A, Weiss TM, Niebuhr M, Pan B, Appleton BA, Wiesmann C, Bazan JF, Fairbrother WJ (October 2009). "Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes". Structure 17 (10): 1398–410. doi:10.1016/j.str.2009.08.009. PMC 2766095. PMID 19836339.
- ↑ "Entrez Gene: Interleukin 33".
- ↑ Yagami A, Orihara K, Morita H, Futamura K, Hashimoto N, Matsumoto K, Saito H, Matsuda A (November 2010). "IL-33 mediates inflammatory responses in human lung tissue cells". Journal of Immunology 185 (10): 5743–50. doi:10.4049/jimmunol.0903818. PMID 20926795.
- ↑ Mirchandani AS, Salmond RJ, Liew FY (August 2012). "Interleukin-33 and the function of innate lymphoid cells". Trends in Immunology 33 (8): 389–96. doi:10.1016/j.it.2012.04.005. PMID 22609147.
- ↑ http://m.pnas.org/content/early/2016/04/13/1604032113.full
- ↑ Baekkevold ES, Roussigné M, Yamanaka T, Johansen FE, Jahnsen FL, Amalric F, Brandtzaeg P, Erard M, Haraldsen G, Girard JP (July 2003). "Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules". The American Journal of Pathology 163 (1): 69–79. doi:10.1016/S0002-9440(10)63631-0. PMC 1868188. PMID 12819012.
- ↑ Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF, Kastelein RA (November 2005). "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". Immunity 23 (5): 479–90. doi:10.1016/j.immuni.2005.09.015. PMID 16286016.
- ↑ Chackerian AA, Oldham ER, Murphy EE, Schmitz J, Pflanz S, Kastelein RA (August 2007). "IL-1 receptor accessory protein and ST2 comprise the IL-33 receptor complex". Journal of Immunology 179 (4): 2551–5. doi:10.4049/jimmunol.179.4.2551. PMID 17675517.
- ↑ Lingel A, Weiss TM, Niebuhr M, Pan B, Appleton BA, Wiesmann C, Bazan JF, Fairbrother WJ (October 2009). "Structure of IL-33 and its interaction with the ST2 and IL-1RAcP receptors--insight into heterotrimeric IL-1 signaling complexes". Structure 17 (10): 1398–410. doi:10.1016/j.str.2009.08.009. PMC 2766095. PMID 19836339.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.