Interleukin-6 Induces Prostaglandin E2 Synthesis in Mouse Astrocytes

被引:23
作者
Chikuma, Toshiyuki [1 ,2 ]
Yoshimoto, Tetsuya [2 ]
Ohba, Masahiro [2 ]
Sawada, Makoto [3 ]
Kato, Takeshi [4 ]
Sakamoto, Tomoaki [5 ]
Hiyama, Yukio [5 ]
Hojo, Hiroshi [2 ]
机构
[1] Showa Pharmaceut Univ, Dept Pharmaceut Analyt Chem, Machida, Tokyo 1948543, Japan
[2] Showa Pharmaceut Univ, Dept Hyg Chem, Machida, Tokyo 1948543, Japan
[3] Nagoya Univ, Dept Brain Life Sci, Environm Med Res Inst, Nagoya, Aichi 4648601, Japan
[4] Yokohama City Univ, Lab Mol Recognit, Grad Sch Integrated Sci, Yokohama, Kanagawa 2360027, Japan
[5] Natl Inst Hlth Sci, Div Drugs, Tokyo 1588501, Japan
关键词
Interleukin-6; Prostaglandin E-2; Cyclooxygenase-2; Soluble interleukin-6 receptor; 130-kDa glycoprotein; Astrocytes; INDUCIBLE CYCLOOXYGENASE; RAT HIPPOCAMPUS; BACTERIAL LIPOPOLYSACCHARIDE; SIGNAL TRANSDUCER; IL-6; RECEPTOR; UP-REGULATION; MICE LACKING; ONCOSTATIN-M; EXPRESSION; NEURONS;
D O I
10.1007/s12031-009-9187-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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 messneger 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.
引用
收藏
页码:175 / 184
页数:10
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