Interleukin-6 prevents dexamethasone-induced myeloma cell death.
Interleukin-6 prevents dexamethasone-induced myeloma cell death.
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DOI：
10.1182/blood.v84.9.3063.bloodjournal8493063
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发表时间：
1994-11
期刊：
影响因子：
20.3
通讯作者：
James W. Hardin;Stewart L. MacLeod;Irina Grigorieva;R. Chang;Bart Barlogie;Huiqing Xiao;J. Epstein
中科院分区：
文献类型：
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作者：
James W. Hardin;Stewart L. MacLeod;Irina Grigorieva;R. Chang;Bart Barlogie;Huiqing Xiao;J. Epstein
本文研究了地塞米松对四种人多发性骨髓瘤细胞系生长的影响。此外，通过使用逆转录聚合酶链反应（RT-PCR）来研究对白细胞介素-6（IL-6）和IL-6受体（IL-6 R）基因表达的影响。地塞米松（Dex）浓度为10（-7）至10（-6）mol/L抑制IL-6基因表达的四个细胞系中的三个，而更高浓度的激素抑制IL-6 R基因表达。地塞米松的作用通过糖皮质激素受体（GR）调节。地塞米松治疗导致与DNA片段化相关的敏感细胞的杀伤，这可以通过与IL-6的伴随治疗来逆转。通过受体核转位或Dex调节的报告基因功能测定，IL-6逆转Dex介导的效应并不是由于GR功能的抑制。这些结果表明，IL-6信号通路的阻断对于Dex有效杀伤骨髓瘤细胞是必不可少的。
The effects of dexamethasone on the growth of four human multiple myeloma cell lines were studied. In addition, the effects on the expression of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) genes were investigated by the use of reverse-transcriptase polymerase chain reaction. Dexamethasone (Dex) concentrations of 10(-7) to 10(-6) mol/L inhibited IL-6 gene expression in three of four cell lines studied, whereas the higher concentration of the hormone inhibited also IL-6R gene expression. Dex effects were modulated through the glucocorticoid receptor (GR). Dex treatment resulted in killing of sensitive cells associated with DNA fragmentation, which could be reversed by concomitant treatment with IL-6. The reversal of Dex-mediated effects by IL-6 did not result from an inhibition of GR function as measured by receptor nuclear translocation or Dex-regulated reporter gene function. These results indicate that blockage of the IL-6 signaling pathway is essential for effective myeloma cell kill by Dex.