Lactoferrin Down-modulates the Activity of the Granulocyte Macrophage Colony-stimulating Factor Promoter in Interleukin-1β-stimulated Cells

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...

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Bibliographic Details
Published in:The Journal of biological chemistry 1995-05, Vol.270 (20), p.12263-12268
Main Authors: Penco, Silvana, Pastorino, Sandra, Bianchi-Scarrà, Giovanna, Garrè, Cecilia
Format: Article
Language:English
Subjects:
Carcinoma - pathology
Cells, Cultured
Depression, Chemical
Fibroblasts - drug effects
Fibroblasts - metabolism
Gene Expression Regulation - drug effects
Genes, Reporter
Genetic Vectors
Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis
Granulocyte-Macrophage Colony-Stimulating Factor - genetics
Humans
Interleukin-1 - pharmacology
Lactoferrin - pharmacology
Lung - embryology
Lymphoma, Large B-Cell, Diffuse - pathology
Promoter Regions, Genetic
Recombinant Fusion Proteins - biosynthesis
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
T-Lymphocytes - drug effects
T-Lymphocytes - metabolism
Transcription, Genetic - drug effects
Transfection
Tumor Cells, Cultured
Urinary Bladder Neoplasms - pathology
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Summary: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-1β. 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-1β-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-1β.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.270.20.12263