Penco S, Pastorino S, Bianchi-Scarrà G, Garrè C
Institute of Biology and Genetics, University of Genova, Italy.
J Biol Chem. 1995 May 19;270(20):12263-8. doi: 10.1074/jbc.270.20.12263.
The human neutrophil lactoferrin (Lf), a cationic iron-binding glycoprotein, has an inhibitor role on granulocyte macrophage colony-stimulating factor (GM-CSF) production via interleukin-1 (IL-1). The nuclear localization of Lf suggests that it may be involved in the transcriptional regulation of GM-CSF gene expression. To explore this possibility, the effect of Lf on GM-CSF gene expression was investigated in various cell lines and in primary cultures of fibroblasts. Down-regulation of GM-CSF mRNA level was observed in Lf-transfected embryonic fibroblasts induced to produce GM-CSF by IL-1 beta. In 5637 cell-line and in embryonic fibroblasts, co-transfection experiments, in which an Lf expression vector was used together with a vector carrying a reporter gene linked to the GM-CSF promoter, revealed that Lf reduces the activity of the GM-CSF promoter. This effect is marked in IL-1 beta-stimulated cells. These findings suggest that Lf plays a negative role in GM-CSF expression at the transcriptional level, perhaps through the mediation of IL-1 beta.
人中性粒细胞乳铁蛋白（Lf）是一种阳离子铁结合糖蛋白，通过白细胞介素-1（IL-1）对粒细胞巨噬细胞集落刺激因子（GM-CSF）的产生具有抑制作用。Lf的核定位表明它可能参与GM-CSF基因表达的转录调控。为了探究这种可能性，我们在各种细胞系和成纤维细胞原代培养物中研究了Lf对GM-CSF基因表达的影响。在经IL-1β诱导产生GM-CSF的Lf转染胚胎成纤维细胞中，观察到GM-CSF mRNA水平下调。在5637细胞系和胚胎成纤维细胞中，共转染实验（其中将Lf表达载体与携带与GM-CSF启动子相连的报告基因的载体一起使用）表明，Lf降低了GM-CSF启动子的活性。这种作用在IL-1β刺激的细胞中很明显。这些发现表明，Lf可能通过IL-1β的介导在转录水平上对GM-CSF表达起负性作用。
