Human lactoferrin suppresses TNF-α-induced intercellular adhesion molecule-1 expression via competition with NF-κB in endothelial cells.
Lactoferrin (Lf) is known to have anti-inflammatory activity, but the mechanisms of action by Lf remain to be elucidated. Here, we demonstrated that TNF-α-induced expression of intercellular adhesion molecule-1 (ICAM-1) was down-regulated by Lf in a DNA-binding dependent manner at transcriptional level in endothelial cells. Our results showed that Lf bound to a DNA region in the ICAM-1 promoter in vitro as well as in chromatin context. Lf inhibited binding of NF-κB to a proximal NF-κB site in ICAM-1 promoter. This type of repression represents an additional mechanism for the action of Lf in regulation of gene expression.
College of Life Science and Graduate School of Biotechnology, Kyung Hee University, Yongin 446-701, Republic of Korea.
Chan Woo
CW
Kim
Tae Hoon
TH
Lee
Keun Hyung
KH
Park
Sang-Yun
SY
Choi
Jiyoung
J
Kim
D001667:Binding, Competitive; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D007781:Lactoferrin / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D004247:DNA; D007781:Lactoferrin