Human lactoferrin activates transcription of IL-1β gene in mammalian cells

Abstract

Lactoferrin (Lf) has been suggested to play roles in primary defense against microbial infection and other cellular processes including immunomodulation. Lf is known to bind to DNA and implicated to activate transcription. In the present study, we demonstrated that Lf stimulated transcription of IL-1β gene, one of natural genes containing putative Lf binding site (LBS) in the 5′-flanking sequences. K562 cells treated with a combination of Lf and PMA showed a synergistic induction in the level of IL-1β mRNA over treatment with PMA alone. Synergistic stimulation of IL-1β expression by Lf and PMA was also confirmed by IL-1β/Luc reporter gene assays. Analysis of Lf domains revealed that the transcriptional domain of Lf is located within the N-terminal 90 amino acids, termed NIa and that the C-terminal half lobe lacked the transactivating activity. The NIa, the N-terminal half lobe as well as intact Lf stimulated transcription of IL-1β gene in the transfected K562 cells along with PMA, while the C-terminal half lobe did not. Our results suggest that Lf may play some roles in transcription of IL-1β gene and may also regulate transcription of other natural genes containing LBS.