Knudsen P J, Dinarello C A, Strom T B
Charles A. Dana Research Institute, Boston, MA.
J Immunol. 1987 Dec 15;139(12):4129-34.
We investigated effects of corticosteroids on interleukin 1 (IL-1) production in monocyte-like tumor cell line, U937. Release of IL-1 activity by bacterial toxin-stimulated cells was completely blocked by 10 nM dexamethasone (Dex). We examined the question whether corticosteroids suppress IL-1 production by blocking transcription of IL-1 mRNA, or by blocking IL-1 synthesis at a post-transcriptional step. Northern blot hybridization analysis indicated that Dex, 10 nM, completely blocked accumulation of IL-1 beta-encoding mRNA in U937 cells. Dex-mediated inhibition of IL-1 release appeared to be glucocorticoid receptor-mediated and was abrogated by progesterone. In addition, Dex at high concentrations could inhibit post-transcriptional synthesis of IL-1 by prestimulated U937 cells. Although Dex, 500 nM, did not change IL-1 mRNA levels in prestimulated cells, it completely blocked IL-1 release and induced a transient increase in cellular cyclic adenosine 3',5'-monophosphate (cAMP) levels. Dex-mediated inhibition of IL-1 release in prestimulated cells is likely to occur via increased levels of cAMP, which have been shown to block post-transcriptional IL-1 synthesis. Our results indicate that glucocorticoids suppress IL-1 synthesis by two distinct mechanisms, blocking transcription of IL-1 mRNA during monocyte activation, and blocking post-transcriptional IL-1 synthesis via cAMP.
我们研究了皮质类固醇对单核细胞样肿瘤细胞系U937中白细胞介素1（IL-1）产生的影响。细菌毒素刺激的细胞释放的IL-1活性被10 nM地塞米松（Dex）完全阻断。我们研究了皮质类固醇是通过阻断IL-1 mRNA的转录，还是在转录后步骤阻断IL-1合成来抑制IL-1产生的问题。Northern印迹杂交分析表明，10 nM的Dex完全阻断了U937细胞中编码IL-1β的mRNA的积累。Dex介导的IL-1释放抑制似乎是由糖皮质激素受体介导的，并被孕酮消除。此外，高浓度的Dex可以抑制预刺激的U937细胞转录后合成IL-1。虽然500 nM的Dex没有改变预刺激细胞中IL-1 mRNA的水平，但它完全阻断了IL-1的释放，并导致细胞环磷酸腺苷（cAMP）水平短暂升高。Dex介导的预刺激细胞中IL-1释放的抑制可能是通过cAMP水平的升高发生的，cAMP已被证明可以阻断转录后IL-1的合成。我们的结果表明，糖皮质激素通过两种不同的机制抑制IL-1的合成，在单核细胞激活过程中阻断IL-1 mRNA的转录，并通过cAMP阻断转录后IL-1的合成。
