Pousset F, Dantzer R, Kelley K W, Parnet P
INSERM U. 394, 1, rue Camille-Saint-Saens, 33077 Bordeaux Cedex, France.
Eur Cytokine Netw. 2000 Sep;11(3):427-34.
Although astrocytes are well known to respond to the pro-inflammatory cytokine, interleukin-1 (IL-1), the receptor and post-receptor mechanisms that mediate IL-1 effects in this cell type are complex and need further investigation. Using electrophoretic mobility shift assay (EMSA), we show that IL-1beta-induced NFkappaB activation in primary culture of mouse astrocytes is mediated by the interaction of this cytokine with the IL-1 type I receptor/IL-1 receptor accessory protein complex, as demonstrated by the ability of blocking monoclonal antibodies against these receptors to attenuate NFkappaB activation. In addition to NFkappaB activation, IL-1beta is also able to phosphorylate Akt, as demonstrated by Western blot. The observation that addition of wortmanin, that specifically blocks Akt phosphorylation, also attenuates NFkappaB activation can be interpreted that Akt phosphorylation interacts with IL-1 signaling pathways. Furthermore, anti-inflammatory cytokines such as IL-4 and IL-10 that block IL-1b-induced NFkappaB activation also attenuate IL-1beta-induced Akt phosphorylation, despite the fact that IL-4 and IL-10 in isolation induced Akt phosphorylation. All these findings point to an interaction between Akt and NFkappaB-dependent IL-1 signaling in the primary culture of astrocytes.
虽然众所周知星形胶质细胞会对促炎细胞因子白细胞介素-1（IL-1）产生反应，但介导IL-1在这种细胞类型中作用的受体及受体后机制很复杂，需要进一步研究。利用电泳迁移率变动分析（EMSA），我们发现，在小鼠星形胶质细胞原代培养物中，IL-1β诱导的核因子κB（NFκB）激活是由该细胞因子与IL-1 I型受体/IL-1受体辅助蛋白复合物相互作用介导的，这通过针对这些受体的阻断性单克隆抗体减弱NFκB激活的能力得以证明。除了NFκB激活外，如蛋白质免疫印迹所示，IL-1β还能够使Akt磷酸化。特异性阻断Akt磷酸化的渥曼青霉素的添加也减弱了NFκB激活，这一观察结果可以解释为Akt磷酸化与IL-1信号通路相互作用。此外，抗炎细胞因子如IL-4和IL-10可阻断IL-1β诱导的NFκB激活，它们也减弱了IL-1β诱导的Akt磷酸化。尽管单独的IL-4和IL-10可诱导Akt磷酸化。所有这些发现都表明在星形胶质细胞原代培养物中Akt与依赖NFκB的IL-1信号之间存在相互作用。
