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: Toshiyuki Chikuma, Tetsuya Yoshimoto, Masahiro Ohba, Makoto Sawada, Takeshi Kato, Tomoaki Sakamoto, Yukio Hiyama, Hiroshi Hojo
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 39 Issue 1-2 Pg. 175-84 (Sep 2009) ISSN: 1559-1166 [Electronic] United States
• PMID: 19277492 (Publication Type: Journal Article)

Chemical References

• Interleukin-6
• Receptors, Interleukin-6
• Cytokine Receptor gp130
• Cyclooxygenase 2
• Dinoprostone

Topics

• Animals
• Astrocytes (cytology, metabolism)
• Cells, Cultured
• Cyclooxygenase 2 (genetics, metabolism)
• Cytokine Receptor gp130 (metabolism)
• Dinoprostone (metabolism)
• Humans
• Interleukin-6 (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Receptors, Interleukin-6 (genetics, metabolism)