Interleukin-6 Induces Prostaglandin E2 Synthesis in Mouse Astrocytes
Interleukin-6 Induces Prostaglandin E2 Synthesis in Mouse Astrocytes
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DOI：
10.1007/s12031-009-9187-6
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发表时间：
2009-09-01
影响因子：
3.1
通讯作者：
Hojo, Hiroshi
中科院分区：
文献类型：
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作者：
Chikuma, Toshiyuki;Yoshimoto, Tetsuya;Hojo, Hiroshi
白细胞介素-6在中枢神经系统（CNS）中的生理功能是复杂的；白细胞介素-6发挥神经营养和神经保护作用，但也可以作为炎症、脱髓鞘和星形胶质细胞形成的介质，这取决于细胞环境。然而，白细胞介素-6在星形胶质细胞中的作用尚不清楚。在本研究中，我们研究了促炎细胞因子白细胞介素-6对小鼠星形胶质细胞中炎症介质前列腺素E-2产生的影响。白细胞介素-6通过快速和短暂诱导环氧化酶-2信使RNA，以时间依赖性的方式刺激前列腺素E-2的产生，随后是环氧化酶-2蛋白的合成。白细胞介素-6可能通过与其特异性可溶性白细胞介素-6受体和130-kDa糖蛋白相互作用而作用于神经系统。白细胞介素-6和可溶性白细胞介素-6受体同时处理星形胶质细胞，可显著诱导前列腺素E-2的合成，这种作用可通过添加可溶性白细胞介素-6受体的中和抗体来抑制。此外，小鼠130-kDa糖蛋白抗体以剂量依赖的方式抑制白介素-6以及白介素-6/可溶性白介素-6受体复合物诱导的前列腺素E-2的形成。这些结果表明，白细胞介素-6/可溶性白细胞介素-6受体复合物和信号换能器130-kDa糖蛋白在小鼠星形胶质细胞中环氧化酶-2的表达和随后前列腺素E-2的形成中发挥重要作用，白细胞介素-6是中枢神经系统免疫和炎症过程的重要调节因子。
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.