Derigs H G, Boswell H S
Third Department of Medicine, Johannes-Gutenberg University, Mainz, Germany.
Leukemia. 1993 Apr;7(4):630-4.
Recent evidence has established an important role for leukemia inhibitory factor (LIF) as hematopoietically active cytokine. The present study utilized two different murine bone marrow stromal cell lines, +/+-1.LDA11 and MBA-13, to define regulatory mechanisms of LIF messenger RNA (mRNA) induction. LIF mRNA was not detected in uninduced stromal cells under serum-free conditions. Incubation with interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha) or the cAMP analogue 8-bromoadenosine 3':5'-monophosphate (8BrcAMP) resulted in weakly induced LIF mRNA. Coincubation of combinations of the stimuli increased LIF mRNA expression additively. LIF mRNA stability, even after stimulation, was low with a half-life of about 30 min, suggesting a functional role for known AU-rich motifs in the 3' untranslated LIF mRNA region in mediating this instability. This possibility was further supported by the ability of cycloheximide to increase mRNA levels without affecting transcription. Transcriptional activation was found to be the main mechanism leading to LIF mRNA expression by IL-1, by TNF-alpha, and by 8BrcAMP. These stimuli appeared to act additively in this regard, suggesting involvement of distinct transcription factors. Induction of transcription was detected 45 min post-stimulation and showed peak levels at 90 min. Kinetics of LIF transcriptional activation showed similarity with the kinetics of the transcription factors, jun-B and c-fos, suggesting a possible role for these proteins or other early response genes in events leading to LIF expression.
最近的证据表明白血病抑制因子（LIF）作为一种具有造血活性的细胞因子发挥着重要作用。本研究利用两种不同的小鼠骨髓基质细胞系，即+/+-1.LDA11和MBA-13，来确定LIF信使核糖核酸（mRNA）诱导的调控机制。在无血清条件下，未诱导的基质细胞中未检测到LIF mRNA。用白细胞介素-1（IL-1）、肿瘤坏死因子-α（TNF-α）或环磷酸腺苷（cAMP）类似物8-溴腺苷3':5'-单磷酸（8BrcAMP）孵育可导致LIF mRNA微弱诱导。刺激组合共同孵育可使LIF mRNA表达呈累加性增加。即使在刺激后，LIF mRNA的稳定性也很低，半衰期约为30分钟，这表明3'非翻译LIF mRNA区域中已知的富含AU基序在介导这种不稳定性中发挥了功能作用。环己酰亚胺能够在不影响转录的情况下增加mRNA水平，这进一步支持了这种可能性。发现转录激活是IL-1、TNF-α和8BrcAMP导致LIF mRNA表达的主要机制。在这方面，这些刺激似乎具有累加作用，提示不同转录因子的参与。刺激后45分钟检测到转录诱导，并在90分钟时达到峰值水平。LIF转录激活的动力学与转录因子jun-B和c-fos的动力学相似，提示这些蛋白质或其他早期反应基因在导致LIF表达的事件中可能发挥作用。
