di Giovine F S, Symons J A, Duff G W
University of Sheffield, Dept. Medicine and Pharmacology, U.K.
Immunol Lett. 1991 Aug;29(3):211-8. doi: 10.1016/0165-2478(91)90172-7.
Interleukin 1 beta (IL1 beta) is an inducible polypeptide with many roles in host defence and homoeostasis. It has also been implicated as a mediator of infectious, inflammatory and autoimmune diseases, and the kinetics of its production are relevant to an understanding of the pathogenesis of these conditions. We report here the time-course of IL1 beta production in human adherent monocytes. Both IL1 beta protein and mRNA were measured following cell activation with bacterial endotoxin (lipopolysaccharide; LPS), and pro-inflammatory crystals of monosodium urate (MSU), which cause arthritis and kidney disease. We also tested other crystal types associated with arthritis, namely hydroxylapatite and calcium pyrophosphate dihydrate. IL1 was absent from unstimulated cells, but IL1 beta mRNA accumulated rapidly after LPS or MSU stimulation and was associated with the later appearance of intracellular IL1 beta protein which was subsequently released from the cells (60% at 9 h). The other crystals failed to induce significant IL1 production. Our findings support the view that production of IL1 beta in human mononuclear cells is based on rapid translation of an inducible pool of mRNA and that no pre-formed mRNA or intracellular protein exists in normal blood monocytes. Further, although IL1 beta is translated without a conventional leader sequence, it is translocated extracellularly with the kinetics of a secretory protein.
白细胞介素1β（IL1β）是一种可诱导的多肽，在宿主防御和体内平衡中发挥多种作用。它还被认为是感染性、炎症性和自身免疫性疾病的介质，其产生的动力学与理解这些疾病的发病机制相关。我们在此报告人黏附单核细胞中IL1β产生的时间进程。在用细菌内毒素（脂多糖；LPS）和导致关节炎和肾脏疾病的尿酸单钠（MSU）促炎晶体激活细胞后，对IL1β蛋白和mRNA进行了测量。我们还测试了与关节炎相关的其他晶体类型，即羟基磷灰石和二水焦磷酸钙。未刺激的细胞中不存在IL1，但LPS或MSU刺激后IL1β mRNA迅速积累，并与随后细胞内IL1β蛋白的出现相关，该蛋白随后从细胞中释放（9小时时为60%）。其他晶体未能诱导显著的IL1产生。我们的研究结果支持这样一种观点，即人单核细胞中IL1β的产生基于可诱导mRNA池的快速翻译，并且正常血液单核细胞中不存在预先形成的mRNA或细胞内蛋白。此外，尽管IL1β在没有常规前导序列情况下进行翻译，但它以分泌蛋白的动力学转运到细胞外。
