Human lactoferrin activates transcription of IL-1beta gene in mammalian cells.
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-1beta 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-1beta mRNA over treatment with PMA alone. Synergistic stimulation of IL-1beta expression by Lf and PMA was also confirmed by IL-1beta/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-1beta 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-1beta gene and may also regulate transcription of other natural genes containing LBS.
Son
Kyung-No
KN
School of Life Science and Biotechnology, Kyung Hee University, Yongin 449-701, Korea.
Park
Junbae
J
Chung
Chan-Keun
CK
Chung
Dae K
DK
Yu
Dae-Yeul
DY
Lee
Kyung-Kwang
KK
Kim
Jiyoung
J
D000818:Animals; D019556:COS Cells; D002273:Carcinogens; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D020014:K562 Cells; D007781:Lactoferrin / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D002273:Carcinogens; D007375:Interleukin-1; D012333:RNA, Messenger; D008156:Luciferases; D015500:Chloramphenicol O-Acetyltransferase; D007781:Lactoferrin; D013755:Tetradecanoylphorbol Acetate