S. Penco et al., LACTOFERRIN DOWN-MODULATES THE ACTIVITY OF THE GRANULOCYTE-MACROPHAGECOLONY-STIMULATING FACTOR PROMOTER IN INTERLEUKIN-1-BETA-STIMULATED CELLS, The Journal of biological chemistry, 270(20), 1995, pp. 12263-12268
The human neutrophil lactoferrin (Lf), a cationic iron-binding glycopr
otein, has an inhibitor role on granulocyte macrophage colony-stimulat
ing factor (GM-CSF) production via interleukin-1 (IL-1). The nuclear l
ocalization of Lf suggests that it may be involved in the transcriptio
nal regulation of GM-CSF gene expression. To explore this possibility,
the effect of Lf on GM-CSF gene expression was investigated in variou
s cell lines and in primary cultures of fibroblasts. Down-regulation o
f GM-CSF mRNA level was observed in Lf-transfected embryonic fibroblas
ts induced to produce GM-CSF by IL-1 beta. In 5637 cell-line and in em
bryonic fibroblasts, co-transfection experiments, in which an Lf expre
ssion vector was used together with a vector carrying a reporter gene
linked to the GM-CSF promoter, revealed that Lf reduces the activity o
f the GM-CSF promoter. This effect is marked in IL-1 beta-stimulated c
ells. These findings suggest that Lf plays a negative role in GM-CSF e
xpression at the transcriptional level, perhaps through the mediation
of IL-1 beta.