Turner M, Chantry D, Buchan G, Barrett K, Feldmann M
Charing Cross Sunley Research Centre, Hammersmith, London.
J Immunol. 1989 Dec 1;143(11):3556-61.
IL-1 gene expression was investigated in human blood mononuclear cells. IL-1 alpha and IL-1 beta mRNA were induced with LPS or TNF. Kinetic measurements on Northern blots revealed that these stimuli elicited qualitatively similar changes in IL-1 mRNA levels, and that expression of IL-1 mRNA was transient. IL-1 beta mRNA was the predominant mRNA species and remained elevated for somewhat longer than IL-1 alpha mRNA. TNF and IFN-gamma synergized to induce both species of IL-1 mRNA and IL-1 bioactivity. Transcriptional control, as measured by nuclear run on assays, partly determines the greater levels of IL-1 beta mRNA because the rate of IL-1 beta transcription was greater than that of IL-1 alpha. Cycloheximide (CHX) was able to induce IL-1 mRNA but did not induce transcription of either IL-1 gene. When added to cultures pretreated with TNF or LPS, CHX superinduced IL-1 mRNA, but IL-1 transcription was not increased. If added simultaneously CHX blocked TNF-induced IL-1 gene transcription, suggesting that TNF may induce factors required for IL-1 gene transcription. CHX increased the stability of both IL-1 alpha and IL-1 beta mRNA, demonstrating the existence of a post-transcriptional form of control. In half-life experiments IL-1 beta mRNA was more stable than IL-1 alpha mRNA, indicating that post-transcriptional control also contributes to the greater steady state levels of IL-1 beta. Taken together, the available evidence suggests IL-1 alpha and IL-1 beta mRNA are regulated differentially at both the transcriptional and post-transcriptional level.
在人血单核细胞中研究了白细胞介素-1（IL-1）基因的表达。用脂多糖（LPS）或肿瘤坏死因子（TNF）诱导IL-1α和IL-1β信使核糖核酸（mRNA）。对Northern印迹进行动力学测量显示，这些刺激在IL-1 mRNA水平上引发了定性相似的变化，并且IL-1 mRNA的表达是短暂的。IL-1β mRNA是主要的mRNA种类，其保持升高的时间比IL-1α mRNA稍长。TNF和干扰素-γ（IFN-γ）协同诱导两种IL-1 mRNA和IL-1生物活性。通过核转录分析测量的转录控制部分决定了IL-1β mRNA的更高水平，因为IL-1β的转录速率大于IL-1α。放线菌酮（CHX）能够诱导IL-1 mRNA，但不诱导任何一种IL-1基因的转录。当添加到用TNF或LPS预处理的培养物中时，CHX超诱导IL-1 mRNA，但IL-1转录没有增加。如果同时添加，CHX会阻断TNF诱导的IL-1基因转录，表明TNF可能诱导IL-1基因转录所需的因子。CHX增加了IL-1α和IL-1β mRNA的稳定性，证明存在转录后形式的调控。在半衰期实验中，IL-1β mRNA比IL-1α mRNA更稳定，表明转录后调控也有助于IL-1β的更高稳态水平。综上所述，现有证据表明IL-1α和IL-1β mRNA在转录和转录后水平上受到不同的调控。
