白细胞介素6激活热休克蛋白90β基因的表达。
Interleukin 6 activates heat-shock protein 90 beta gene expression.
作者信息
Stephanou A, Amin V, Isenberg D A, Akira S, Kishimoto T, Latchman D S
机构信息
Department of Molecular Pathology, University College London Medical School, U.K.
出版信息
Biochem J. 1997 Jan 1;321 ( Pt 1)(Pt 1):103-6. doi: 10.1042/bj3210103.
Abstract
The levels of the cytokine interleukin-6 (IL-6) and the heat-shock protein hsp90 have both been reported to be elevated in patients with active systemic lupus erythematosus (SLE). We show that hsp90 protein accumulates to increased levels in both HuH7 hepatoma cells and peripheral blood mononuclear cells (PBMCs) treated with IL-6. In PBMCs this effect occurs without induction of the other hsps, paralleling the specific elevation of hsp90 in SLE. IL-6 is able to activate the hsp90 gene promoter directly; this activation can also be achieved by overexpressing either of the transcription factors NF-IL-6 or NF-IL-6 beta whose synthesis is induced by IL-6 treatment. Hence the induction of hsp90 protein accumulation by IL-6 is likely to be dependent on the enhanced activity of the hsp90 beta gene promoter produced by increased levels of NF-IL-6 and/or NF-IL-6 beta. These effects are discussed in terms of the role of hsp90 in the normal immune system and the mechanism of its activation in patients with SLE.
摘要
据报道，细胞因子白细胞介素-6（IL-6）和热休克蛋白hsp90的水平在活动性系统性红斑狼疮（SLE）患者中均升高。我们发现，在用IL-6处理的HuH7肝癌细胞和外周血单核细胞（PBMC）中，hsp90蛋白积累至升高水平。在PBMC中，这种效应在未诱导其他热休克蛋白的情况下发生，这与SLE中hsp90的特异性升高相似。IL-6能够直接激活hsp90基因启动子；通过过表达转录因子NF-IL-6或NF-IL-6β中的任何一种也可实现这种激活，它们的合成由IL-6处理诱导。因此，IL-6诱导hsp90蛋白积累可能依赖于NF-IL-6和/或NF-IL-6β水平升高所产生的hsp90β基因启动子活性增强。本文根据hsp90在正常免疫系统中的作用及其在SLE患者中的激活机制对这些效应进行了讨论。
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