Pousset F, Cremona S, Dantzer R, Kelley K W, Parnet P
INSERM U.394, Institut F. Magendie, Bordeaux, France.
J Neurochem. 2001 Feb;76(3):901-9. doi: 10.1046/j.1471-4159.2001.00103.x.
Brain astrocytes play a pivotal role in the brain response to inflammation. They express IL-1 receptors including the type I IL-1 receptor (IL-1RI) that transduces IL-1 signals in cooperation with the IL-1 receptor accessory protein (IL-1RAcP) and the type II IL-1 receptor (IL-1RII) that functions as a decoy receptor. As glucocorticoid receptors are expressed on astrocytes, we hypothesized that glucocorticoids regulate IL-1 receptors expression. IL-1beta-activated mouse primary astrocytes were treated with 10(-6) M dexamethasone, and IL-1 receptors were studied at the mRNA and protein levels. Using RT-PCR, IL-1RI and IL-1RII but not IL-1RAcP mRNAs were found to be up-regulated by dexamethasone in a time-dependent manner. Dexamethasone (Dex), but not progesterone, had no effect on IL-1RI but strongly increased IL-1RII mRNA expression. Binding studies revealed an increase in the number of IL-1RII binding sites under the effect of Dex, but no change in affinity. These findings support the concept that glucocorticoids have important regulatory effect on the response of astrocytes to IL-1.
脑星形胶质细胞在大脑对炎症的反应中起关键作用。它们表达白细胞介素-1（IL-1）受体，包括与IL-1受体辅助蛋白（IL-1RAcP）协同转导IL-1信号的I型IL-1受体（IL-1RI）和作为诱饵受体发挥作用的II型IL-1受体（IL-1RII）。由于星形胶质细胞上表达糖皮质激素受体，我们推测糖皮质激素调节IL-1受体的表达。用10^(-6) M地塞米松处理IL-1β激活的小鼠原代星形胶质细胞，并在mRNA和蛋白质水平研究IL-1受体。使用逆转录聚合酶链反应（RT-PCR）发现，地塞米松以时间依赖性方式上调IL-1RI和IL-1RII的mRNA，但不影响IL-1RAcP的mRNA。地塞米松（Dex）而非孕酮对IL-1RI无影响，但强烈增加IL-1RII的mRNA表达。结合研究表明，在地塞米松作用下，IL-1RII结合位点数量增加，但亲和力无变化。这些发现支持糖皮质激素对星形胶质细胞对IL-1反应具有重要调节作用这一概念。
