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

• 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
• ISSN: 0021-9258; 1083-351X
• 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-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.