Cytokine regulation of human microglial cell IL-8 production.
Cytokine regulation of human microglial cell IL-8 production.
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DOI：
10.4049/jimmunol.160.4.1944
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发表时间：
1998-02
影响因子：
4.4
通讯作者：
L. Ehrlich;Shuxian Hu;W. Sheng;Richard Sutton;G. Rockswold;Phillip K. Peterson;Chun C. Chao
中科院分区：
文献类型：
--
作者：
L. Ehrlich;Shuxian Hu;W. Sheng;Richard Sutton;G. Rockswold;Phillip K. Peterson;Chun C. Chao
IL-8 参与中性粒细胞激活和趋化作用，可能对继发于脑膜炎、脑炎和创伤性损伤的中枢神经系统炎症反应很重要。然而，在这些炎症过程中大脑内 IL-8 的来源尚不清楚。为了探索小胶质细胞在 IL-8 产生中的作用，用 LPS 以及促炎和抗炎细胞因子处理人类胎儿小胶质细胞（大脑中常驻的巨噬细胞），以确定它们对 IL-8 产生的影响。我们发现，IL-8 蛋白水平随着 LPS 或 IL-1 beta 或 TNF-α 的升高而增加，这也与 RT-PCR 检测到的 IL-8 mRNA 水平升高相对应。用 IL-4、IL-10 或 TGF-β1 预处理可有效抑制这些促炎剂的刺激作用。这些发现表明，人类小胶质细胞响应促炎刺激而合成 IL-8，而抗炎细胞因子会下调这种趋化因子的产生。这些结果可能对某些涉及炎症的中枢神经系统损伤具有重要的治疗意义。
IL-8 involvement in neutrophil activation and chemotaxis may be important in inflammatory responses within the central nervous system, secondary to meningitis, encephalitis, and traumatic injury. The source of IL-8 within the brain during these inflammatory processes, however, is unknown. To explore the role of microglia in the production of IL-8, human fetal microglia, which are the resident macrophages of the brain, were treated with LPS and pro- and anti-inflammatory cytokines to determine their effects on IL-8 production. We found that IL-8 protein levels increased in response to LPS or IL-1 beta, or to TNF-alpha, which also corresponded to elevated IL-8 mRNA levels by RT-PCR. Pretreatment with IL-4, IL-10, or TGF-beta 1 potently inhibited the stimulatory effects of these proinflammatory agents. These findings indicate that human microglia synthesize IL-8 in response to proinflammatory stimuli, and that anti-inflammatory cytokines down-regulate the production of this chemokine. These results may have important therapeutic implications for certain central nervous system insults involving inflammation.