title: Production and functions of IL-33 in the central nervous system.
abstract: Interleukin-33 (IL-33) is a novel multifunctional IL-1 family cytokine. IL-33 signals via a heterodimer composed of IL-1 receptor-related protein ST2 and IL-1 receptor accessory protein (IL-1RAcP). IL-33 has been shown to activate T helper 2 cells (Th2), mast cells and basophils to produce a variety of Th2 cytokines and mediate allergic-type immune responses. Recent studies have revealed that glial cells are induced to express IL-33 mRNA and protein. However, the functions of IL-33 and its producing cells in the central nervous system (CNS) are still uncertain. In this study, we investigated the expression and function of IL-33 in the CNS. IL-33 is produced by endothelial cells and astrocytes but not by microglia or neurons. The IL-33 receptors are expressed mainly in microglia and astrocytes. IL-33 dose-dependently induces the proliferation of microglia and enhances the production of pro-inflammatory cytokines, such as IL-1β and TNFα, as well as the anti-inflammatory cytokine IL-10. It also enhances chemokines and nitric oxide production and phagocytosis by microglia. Thus, IL-33 produced in the CNS activates microglia and may function as a pro-inflammatory mediator in the pathophysiology of the CNS.
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Yasuoka
authors.forename: Jun
authors.initials: J
authors.lastname: Kawanokuchi
authors.forename: Bijay
authors.initials: B
authors.lastname: Parajuli
authors.forename: Shijie
authors.initials: S
authors.lastname: Jin
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Doi
authors.forename: Mariko
authors.initials: M
authors.lastname: Noda
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sonobe
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizuno
authors.forename: Akio
authors.initials: A
authors.lastname: Suzumura
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D000067596:Interleukin-33; D007378:Interleukins / Q000096:biosynthesis* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism / Q000473:pathology
chemical_list: C506535:Il33 protein, mouse; D018836:Inflammation Mediators; D000067596:Interleukin-33; D007378:Interleukins