title: Interleukin-6 induces prostaglandin E(2) synthesis in mouse astrocytes.
abstract: The physiological function of interleukin-6 within the central nervous system (CNS) is complex; interleukin-6 exerts neurotrophic and neuroprotective effects and yet can also function as a mediator of inflammation, demyelination, and astrogliosis depending on the cellular context. However, the roles of interleukin-6 in astrocytes are poorly understood. In the present study, we investigated the effect of the pro-inflammatory cytokine interleukin-6 on the production of the inflammatory mediator prostaglandin E(2) in mouse astrocytes. Interleukin-6 stimulated prostaglandin E(2) production in a time-dependent fashion via a rapid and transient induction of cyclooxygenase-2 messenger RNA, followed by cyclooxygenase-2 protein synthesis. Interleukin-6 may act on the nervous system by interacting with its specific soluble interleukin-6 receptor and the signal transducer 130-kDa glycoprotein. Simultaneous treatment of astrocytes with interleukin-6 and soluble interleukin-6 receptor caused marked induction of prostaglandin E(2) synthesis, and this effect was suppressed by adding a neutralizing antibody against soluble interleukin-6 receptor. Furthermore, the mouse 130-kDa glycoprotein antibody suppressed prostaglandin E(2) formation induced by interleukin-6, as well as interleukin-6/soluble interleukin-6 receptor complexes, in a dose-dependent manner. These results indicate that interleukin-6/soluble interleukin-6 receptor complexes and the signal transducer 130-kDa glycoprotein play an important role in the regulation of cyclooxygenase-2 expression and subsequent prostaglandin E(2) formation in mouse astrocytes and that interleukin-6 is an important regulator of immune and inflammatory processes in the CNS.
authors.affiliation: Department of Hygienic Chemistry, Showa Pharmaceutical University, Machida-shi, Tokyo 194-8543, Japan. chikuma@ac.shoyaku.ac.jp
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Chikuma
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ohba
authors.forename: Makoto
authors.initials: M
authors.lastname: Sawada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kato
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Sakamoto
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hojo
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D050822:Cytokine Receptor gp130 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D051546:Cyclooxygenase 2; D015232:Dinoprostone