Interleukin-6 induces prostaglandin E(2) synthesis in mouse astrocytes.
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.
Chikuma
Toshiyuki
T
Department of Hygienic Chemistry, Showa Pharmaceutical University, Machida-shi, Tokyo 194-8543, Japan. chikuma@ac.shoyaku.ac.jp
Yoshimoto
Tetsuya
T
Ohba
Masahiro
M
Sawada
Makoto
M
Kato
Takeshi
T
Sakamoto
Tomoaki
T
Hiyama
Yukio
Y
Hojo
Hiroshi
H
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
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130; D051546:Cyclooxygenase 2; D015232:Dinoprostone